FOR PROPOSED PHARMA & PHARMA INTERMEDIATES MANUFACTURING...

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FORM-1

FOR

PROPOSED PHARMA & PHARMA INTERMEDIATES

MANUFACTURING UNIT

OF

M/s. KESHAV INTERCHEM

PLOT NO. 905/11/8, GIDC ESTATE,

PANOLI-394 116, TALUKA: ANKLESHWAR,

DISTRICT: BHARUCH, GUJARAT

Prepared by:

Aqua-Air Environmental Engineers Pvt. Ltd.

(Pollution Control Consultants & Engineers)

Reg. Office: 403, Centre Point, Nr. Kadiwala School, Ring Road,

Surat – 395 002, Gujarat, India Fax: +91 261 2707273 / 3987273

Tel: + 91 261 3048586 / 2460854 / 2461241

E-mail: [email protected] Visit us at: www.aqua-air.co.in

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APPENDIX I

(See paragraph - 6)

FORM 1

Sr.

No.

Item Details

1. Name of the project/s M/s. Keshav Interchem

2. S. No. in the schedule 5 (f)

3. Proposed capacity/area/length/tonnage

to be handled/command area/lease

area/number of wells to be drilled

Proposed Capacity = 15 MT/Month

Total Plot Area = 2,767.18 m2

4. New/Expansion/Modernization New

5. Existing Capacity/Area etc. For detail Please refer Annexure – I

6. Category of Project i.e. ‘A’ or ‘B’ ‘A’

7. Does it attract the general condition? If

yes, please specify.

Yes. Located within 5 km of critically

polluted area (Ankleshwar).

8. Does it attract the specific condition? If

yes, please specify.

No

Location

Plot/Survey/Khasra No. Plot No. 905/11/8

Village GIDC estate, Panoli

Tehsil Ankleshwar

District Bharuch

9.

State Gujarat

10. Nearest railway station/airport along

with distance in kms.

Railway Station: Ankleshwar (4.5 km)

Airport: Surat (60 km)

11. Nearest Town, city, District

Headquarters along with distance in

kms.

Panoli Village (3 km)

Bharuch (15.5 km)

12. Village Panchayats, Zilla Parishad,

Municipal Corporation, local body

(complete postal address with

telephone nos. to be given)

Notified Area Authority, Panoli

13. Name of the applicant M/s. Keshav Interchem

14. Registered Address Plot No. 905/11/8, GIDC estate,

Panoli-394116, Taluka: Ankleshwar,

District: Bharuch, Gujarat

Address for correspondence:

Name Ms. Rutu Mahendrabhai Patel

Designation (Owner/Partner/CEO) Proprietor

15.

Address M/s. Keshav Interchem

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A-1/32, Nirman complex, R. C.

Technical Road, Chankyapuri,

Ghatlodia, Ahmadabad- 386001 (Guj.)

Pin Code 386001

E-mail [email protected]

Telephone No. --

Fax No. --

Mobile No. +919429437733, +917203055448

16. Details of Alternative Sites examined, if

any.

Location of these sites should be shown

on a topo sheet.

NA

17. Interlinked Projects No

18. Whether separate application of

interlinked project has been submitted?

No

19. If yes, date of submission No

20. If no, reason No

21. Whether the proposal involves

approval/clearance under: if yes, details

of the same and their status to be

given.

(a) The Forest (Conservation) Act, 1980?

(b) The Wildlife (Protection) Act, 1972?

(c) The C.R.Z. Notification, 1991?

No

22. Whether there is any Government

Order/Policy relevant/relating to the

site?

No

23. Forest land involved (hectares) No

24. Whether there is any litigation pending

against the project and/or land in which

the project is propose to be set up?

(a) Name of the Court

(b) Case No.

(c) Orders/directions of the Court, if any

and its relevance with the proposed

project.

No

• Capacity corresponding to sectoral activity (such as production capacity for

manufacturing, mining lease area and production capacity for mineral production,

area for mineral exploration, length for linear transport infrastructure, generation

capacity for power generation etc.,)

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(II) Activity

1. Construction, operation or decommissioning of the Project involving actions, which will cause physical changes in the locality (topography, land use, changes in water bodies, etc.)

Sr.

No.

Information/Checklist confirmation Yes

/No

Details thereof with approximate

quantities frates, wherever

possible) with source of information

data

1.1 Permanent or temporary change in land use, land cover or topography including increase intensity of land use (with respect to local land use plan)

No Proposed project activity is within the Panoli GIDC Industrial Estate.

1.2 Clearance of existing land,

vegetation and Buildings?

Yes Minor site clearance activities shall be carried out to clear shrubs and weed.

1.3 Creation of new land uses?

No The project site is located on level ground, which does not require any major land filling for area grading work.

1.4 Pre-construction investigations e.g.

bore Houses, soil testing?

No Proposed site is located within earmarked industrial estate developed by GIDC.

1.5 Construction works? Yes Please refer Annexure – I.

1.6 Demolition works? No There will be not any demolition work at the site.

1.7 Temporary sites used for

construction works or housing of

construction workers?

No Proposed site is located within notified industrial estate developed by GIDC and all required manpower will be employed from nearby area.

1.8 Above ground buildings, structures

or earthworks including linear

structures, cut and fill or excavations

Yes Please refer Annexure – I.

1.9 Underground works mining or

tunneling?

No Not Required

1.10 Reclamation works? No Not Required

1.11 Dredging? No Not Required

1.12 Off shore structures? No Not Required

1.13 Production and manufacturing

processes?

Yes Please refer Annexure – III.

1.14 Facilities for storage of goods or

materials?

Yes Areas for storage of raw materials and finished products will be developed.

1.15 Facilities for treatment or disposal of

solid waste or liquid effluents?

Yes For Facilities for treatment & disposal of liquid effluents please refer Annexure – V. For Hazardous waste details please refer Annexure – VII.

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1.16 Facilities for long term housing of

operational workers?

No Not Concerned

1.17 New road, rail or sea traffic during

Construction or operation?

No There will be very minor traffic increase due to proposed project and will not cause any change in locality.

1.18 New road, rail, air waterborne or

other transport infrastructure

including new or altered routes and

stations, ports, airports etc?

No Proposed site is located within notified industrial estate having very well developed infrastructure facilities. Therefore, there will not be any need of new transportation route/station.

1.19 Closure or diversion of existing

transport routes or infrastructure

leading to changes in Traffic

movements?

No Not Applicable

1.20

New or diverted transmission lines or

Pipelines?

No Proposed site is situated in notified industrial estate having very well developed transmission lines or pipelines for resources and effluent handling. Therefore, there will not be any need of new or diverted transmission lines or pipelines.

1.21 Impoundment, damming, culverting,

realignment or other changes to the

hydrology of watercourses or

aquifers?

No Water required will be met through GIDC Water Supply.

1.22 Stream crossings? No Not Required

1.23 Abstraction or transfers of water

form ground or surface waters?

Yes Water requirement will be met through Panoli GIDC water supply.

1.24 Changes in water bodies or the land

surface affecting drainage or run-off?

No Not Concerned

1.25 Transport of personnel or materials

for construction, operation or

decommissioning?

Yes Transportation of personnel or raw material and products will be primarily by road only.

1.26 Long-term dismantling or

decommissioning or restoration

works?

No Not Required

1.27 Ongoing activity during

decommissioning which could have

an impact on the environment?

No Not Concerned

1.28 Influx of people to an area either

temporarily or permanently?

Yes Direct/Indirect employment shall be provided for proposed operation.

1.29 Introduction of alien species? No Not Concerned

1.30 Loss of native species or genetic

diversity?

No Not Concerned

1.31 Any other actions? No Not Concerned

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2. Use of Natural resources for construction or operation of the Project (such as land, water, materials or energy, especially any resources which are non-renewable or in short supply):

Sr.

No.

Information/checklist confirmation Yes/

No

Details thereof (with approximate

quantities /rates, wherever

possible) with source of information

data

2.1 Land especially undeveloped or

agricultural land (ha)

No Proposed project activity will be

within GIDC Industrial Area, Panoli,

District: Bharuch, Gujarat.

2.2 Water (expected source & competing

users) unit: KLD

Yes Water Source: Panoli GIDC Water

Supply. For details please refer

Annexure – IV.

2.3 Minerals (MT) No Not Required

2.4 Construction material – stone,

aggregates, and / soil

(expected source – MT)

Yes Construction materials, like steel,

cement, crushed stones, sand,

rubble, etc. required for the project

shall be procured from the local

market of the region.

2.5 Forests and timber (source – MT) No Not Required

2.6 Energy including electricity and fuels

(source, competing users) Unit: fuel

(MT), energy (MW)

Yes Power required will be 400 KVA

Source: DGVCL

Note: DG Set 100 KVA will be kept

for emergency power back up.

Fuel Requirement:

Natural Gas = 500 SM3/Day

Diesel = 50 Liter/Day

2.7 Any other natural resources

(use appropriate standard units)

No Not Required

3. Use, storage, transport, handling or production of substances or materials, which could

be harmful to human health or the environment or raise concerns about actual or

perceived risks to human health.

Sr.

No.

Information/Checklist confirmation Yes/

No

Details there of (with approximate

quantities/rates, wherever possible)

with source of information data

3.1 Use of substances or materials, which

are hazardous (as per MSIHC rules) to

human health or the environment

(flora, fauna, and water supplies)

Yes Please refer Annexure – VIII.

3.2 Changes in occurrence of disease or

affect disease vectors (e.g. insect or

water borne diseases)

No Not Required

3.3 Affect the welfare of people e.g. by

changing living conditions?

No The project will bring direct / indirect

employment opportunity, which will

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enhance the socio-economic status

of the area.

3.4 Vulnerable groups of people who

could be affected by the project e.g.

hospital patients, children, the

elderly etc.

No Proposed site is located within

notified industrial estate developed

by GIDC.

3.5 Any other causes No Not Required

4. Production of solid wastes during construction or operation or decommissioning

(MT/month)

Sr.

No.


No




4.1 Spoil, overburden or mine wastes No Not Applicable

4.2 Municipal waste (domestic and or

commercial wastes)

Yes Through Septik Tank / Soak Pit

4.3 Hazardous wastes (as per Hazardous

Waste Management Rules)

Yes Please refer Annexure – VII.

4.4 Other industrial process wastes Yes Please refer Annexure – VII.

4.5 Surplus product No

There will not be any surplus

product.

4.6 Sewage sludge or other sludge from

effluent treatment Yes

Please refer Annexure – VII.

4.7 Construction or demolition wastes

Yes

Construction waste shall be utilized

for leveling, land filling in the

premises.

4.8 Redundant machinery or equipment No

All machinery / equipment will be

installed as per requirement.

4.9 Contaminated soils or other

materials No Not Concerned

4.10 Agricultural wastes No Not Concerned

4.11 Other solid wastes Yes

Please refer Annexure – VII.

5. Release of pollutants or any hazardous, toxic or noxious substances to air (Kg/hr)

Sr.

No.


No




5.1 Emissions from combustion of fossil

fuels from stationary or mobile

sources

Yes Please refer Annexure – VI.

5.2 Emissions from production processes Yes Please refer Annexure – VI.

5.3 Emissions from materials handling

storage or transport

Yes Solid raw materials shall be charged

through close pipeline into reactors

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and the dust collection hopper shall

be connected to a bag filter and ID

fan.

5.4 Emissions from construction

activities including plant and

equipment

Yes During construction work, only dust

contamination will be there & water

sprinklers shall be utilized whenever

necessary.

5.5 Dust or odours from handling of

materials including construction

materials, sewage and waste

No Dust from drying will be collected in

to dust collector through cyclone

separator & recovered powder will

be recycled back to process. Air

Handling Unit will be provided where

ever applicable.

5.6 Emissions from incineration of waste

No There will not be incineration of

waste.

5.7 Emissions from burning of waste in

open air e.g. slash materials,

construction debris)

No

No open burning will be carried out

within premises.

5.8 Emissions from any other sources Yes Please refer Annexure – VI.

6. Generation of Noise and Vibration, and Emissions of Light and Heat:

Sr.

No.


No



with source of information data with

source of information data

6.1 From operation of equipment e.g.

engines, ventilation plant, crushers

Yes The Noise level will be within the

prescribed limit. At noisy areas

adequate preventive & control

measures will be taken. No

significant noise, vibration or

emission of light & heat from the

unit.

6.2 From industrial or similar processes Yes All machinery / equipment shall be

well maintained, shall be proper

foundation with anti vibrating pads

wherever applicable and noise levels

within permissible limits.

Acoustic enclosures shall be provided 6.3 From construction or demolition No Minor noise will be generated during

construction work.

6.4 From blasting or piling No No blasting or pilling will be carried

out at project site.

6.5 From construction or operational

traffic

No Not Concerned

6.6 From lighting or cooling systems No Not Concerned

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6.7 From any other sources No Not Concerned 7. Risks of contamination of land or water from releases of pollutants into the ground or

into sewers, surface waters, groundwater, coastal waters or the sea:

Sr.

No.


No




7.1 From handling, storage, use or

spillage of hazardous materials


7.2 From discharge of sewage or other

effluents to water or the land

(expected mode and place of

discharge)

Yes Sewage shall be treated in Septic

Tank / Soak Pit.

For details please refer Annexure – V.

7.3 By deposition of pollutants emitted

to air into the and or into water

No Not Concerned

7.4 From any other sources No Not Concerned

7.5 Is there a risk of long term build up of

pollutants in the environment from

these sources?

No Not Concerned

8. Risk of accidents during construction or operation of the Project, which could affect

human health or the environment

Sr.

No.


No




8.1 From explosions, spillages, fires etc

from storage, handling, use or

production of hazardous substances


8.2 From any other causes No Not Concerned

8.3 Could the project be affected by

natural disasters causing

environmental damage (e.g. floods,

earthquakes, landslides, cloudburst

etc)?

No Not Concerned

9. Factors which should be considered (such as consequential development) which could lead to environmental effects or the potential for cumulative impacts with other existing or planned activities in the locality

Sr. No.

Information/Checklist confirmation

Yes/ No




9.1 Lead to development of supporting. utilities, ancillary development or development stimulated by the project which could have impact on

Yes Please refer Annexure – IX.

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the environment e.g. • Supporting infrastructure (roads, power supply, waste or waste water treatment, etc.)

• housing development • extractive industry • supply industry • other

9.2 Lead to after-use of the site, which

could have an impact on the

environment

No Not Concerned

9.3 Set a precedent for later

developments

No Not Concerned

9.4 Have cumulative effects due to

proximity to other existing or

planned projects with similar effects

No Not Concerned

(III) Environmental Sensitivity

Sr.

No.

Areas Name/

Identity

Aerial distance (within 5 km)

Proposed project location boundary

1 Areas protected under international

conventions, national or local

legislation for their ecological,

landscape, cultural or other related

value

No No protected area within 5 km from

the proposed project site.

2 Areas which important for are or

sensitive Ecol logical reasons -

Wetlands, watercourses or other

water bodies, coastal zone,

biospheres, mountains, forests

Yes River Narmada = 11 km

3 Area used by protected, important or

sensitive Species of flora or fauna for

breeding, nesting, foraging, resting,

over wintering, migration

No Not Concerned

4 Inland, coastal, marine or

underground waters

No Not Concerned

5 State, National boundaries No No state or national boundary falls

within 5 km aerial distance from the

project site.

6 Routes or facilities used by the public

for access to recreation or other

tourist, pilgrim areas.

Yes Public transportation

7 Defense installations Yes Ankleshwar

8 Densely populated or built-up area Yes Panoli village 3 km and Ankleshwar

City around 4.5 km from the

proposed project site.

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9 Area occupied by sensitive man-made

land uses Hospitals, schools, places of

worship, community facilities)

No Not Applicable

10 Areas containing important, high

quality or scarce resources (ground

water resources, surface resources,

forestry, agriculture, fisheries,

tourism, minerals)

No Not Concerned

11 Areas already subjected to pollution

environmental damage. (those where

existing legal environmental standards

are exceeded)

Yes Ankleshwar

12 Areas susceptible to natural hazard

which could cause the project to

present environmental problems

(earthquakes, subsidence, landslides,

flooding erosion, or extreme or

adverse climatic conditions)

No Not Applicable

IV). Proposed Terms of Reference for EIA studies: Please refer Annexure - X

I hereby given undertaking that, the data and information given in the application and

enclosures are true to the best of my knowledge and belief and I am aware that if any part of

the data and information submitted is found to be false or misleading at any stage the project

will be rejected and clearance give, if any to the project will be revoked at our risk and cost.

Date: August 6, 2017

Place: GIDC, Panoli

NOTE:

1. The projects involving clearance under Coastal Regulation Zone Notification, 1991 shall

submit with the application a C.R.Z. map duly demarcated by one of the authorized agencies,

showing the project activities, w.r.t. C.R.Z. (at the stage of TOR) and the recommendations of

the State Coastal Zone Management Authority (at the stage of EC). Simultaneous action shall

also be taken to obtain the requisite clearance under the provisions of the C.R.Z. Notification,

1991 for the activities to be located in the CRZ.

2. The projects to be located within 10 km of the National Parks, Sanctuaries, Biosphere

Reserves, Migratory Corridors of Wild Animals, the project proponent shall submit the map

duly authenticated by Chief Wildlife Warden showing these features vis-à-vis the project

location and the recommendations or comments of the Chief Wildlife Warden thereon (at the

stage of EC).

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3. All correspondence with the Ministry of Environment & Forests including submission of

application for TOR/Environmental Clearance, subsequent clarifications, as may be required

from time to time, participation in the EAC Meeting on behalf of the project proponent shall

be made by the authorized signatory only. The authorized signatory should also submit a

document in support of his claim of being an authorized signatory for the specific project.

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LIST OF ANNEXURES

SR. NO. NAME OF ANNEXURE

I Layout Map of the Plant

II List of Products and Raw materials along with their Production Capacity

III Brief Manufacturing Process Description

IV Details of water consumption & waste water generation

V Details of Effluent Treatment Scheme

VI Details of Air Pollution Control System

VII Details of Hazardous Waste Generation and Disposal

VIII Details of Hazardous Chemicals Storage & Handling

IX Socio-economic Impacts

X Proposed Terms of Reference

XI Copy of Plot Allotment Letter

XII Copy of GIDC Water Supply Certificate

XIII Membership Certificate of CETP (M/s. PETL)

XIV Membership Certificate of Common Solid Waste Disposal Facility & Common

Incineration Facility (M/s. BEIL)

XV Toposheet

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ANNEXURE - I

___________________________________________________________________________

LAYOUT OF MAP OF THE PLANT

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ANNEXURE - II

____________________________________________________________________________

LIST OF PRODUCTS ALONG WITH THEIR PRODUCTION CAPACITY

SR.

NO. PRODUCT NAME CAS NO.

QUANTITY

MT / MONTH

Group – I

1 Phenylephrine hcl AND/OR 61-76-7

2 Ofloxacin AND/OR 82419-36-1

3 Olanzapine AND/OR 132539-06-1

4 Hydrochlorothiazide AND/OR 58-93-5

5 Oxcarbazepine AND/OR 28721-07-5

6 10-Methoxy-5H-dibenz[b,f]azepine-5-

carbonylchloride, 10-Methoxyiminostilbene-5-

carbonylchloride AND/OR

28721-08-6

7 Diclofenac sodium AND/OR 15307-79-6

8 2,6 – dichloro diphenyl amine (dcdpa) AND/OR 15307-93-4

9 N-chloroacetyl-n-phenyl-2,6-dichloro aniline

(cpdca) AND/OR

15308-01-7

10 Indolenone [ (n-1) of dicofenac ] AND/OR 15362-40-0

11 2-Hydroxymethyl-3-methyl-4-(3-methoxy

propanoxyl)pyridine HCL AND/OR

153259-31-5

12 1,2-benisoxazole-3-acetica acid AND/OR 37924-67-7

13 Cis-tosylate AND/OR 134071-44-6

14 Atorvastatin calcium AND/OR 134523-03-8

15 tert-Butyl (4R,6R)-2-[[[6-(2-4-fluorophenyl)-5-

isopropyl-3-phenyl-4-(phenylcarbamoyl)pyrrol-1-

yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate

AND/OR

65564-05-8

16 Nebivolol Hydrochloride AND/OR 152520-56-4

17 Pantaprazol Sodium AND/OR 138786-67-1

18 5-(Difluoromethoxy)-2- {[( 3,4Dimethoxypyridin - 2-

yl) methyl]thio}-1H-benzimidazolee AND/OR

102625-64-9

19 N-((4-Chloromethyl)-2-Thiozolyl)Guanidine

Hydrochloride AND/OR

84545-70-0

20 Methyl 3-amino-2 butenoate AND/OR 14205-39-1

21 2,4-Difluoro-2-(1h- 1,2,4-Triazole-1-Yl)

Acetophenone (Dfta) AND/OR

86404-63-9

22 cis-2-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-

ylmethyl)-1,3-dioxolan-4-ylmethyl methane

67914-86-7

7.0

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SR.


QUANTITY

MT / MONTH

sulphonate AND/OR

23 1-(4-Methoxyphenyl)-1-(4-nitrophenyl) piperazine

AND/OR

74852-61-2

24 2-[[4-(2-Methoxyethyl)phenoxy]methyl-oxirane

AND/OR

56718-70-8

25 3''-acetyl-2''-hydroxy-4-(4 phenylbutoxy)

benzanilide AND/OR

136450-06-1

Group – II

26 Prasugrel Hydrochloride AND/OR 389574-19-0

27 5-[2-Cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl] -

5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one

AND/OR

150322-38-6

28 Dabigatran AND/OR 211915-06-9

29 Femotidine AND/OR 76824-35-6

30 N-[(2'-Cyano[1,1'-biphenyl]-4-yl)methyl]-L valine

methyl ester AND/OR

137863-89-9

31 Amlodipin besylate AND/OR 111470-99-6

32 Amlodipine base AND/OR 88150-42-9

33 2,4-dihydro-4-[(4-(4-hydroxyphenyl)-1-

piperazinyl)phenyl]-2-(1-methylpropyl)-3h-1,2,4-

triazole-3-one AND/OR

106461-41-0

34 Metoprolol tartrate AND/OR 56392-17-7

35 1-(Isopropylamino)-3-[4-(2-methoxyethyl)

phenoxy]-2-propanol AND/OR

37350-58-6

36 Metoprolol succinate AND/OR 98418-47-4

37 Ketoconazole AND/OR 65277-42-1

38 Phthaloyl amlodipine AND/OR 88150-62-3

39 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-

piperazinyl]phenyl]-2-(1-methylpropyl)-3H-1,2,4-

triazol-3-one AND/OR

252964-68-4

5.0

Group – III

40 Montelukast sodium AND/OR 151767-02-1

41 Valsartan AND/OR 137862-53-4

42 Venlafaxine Hydrochloride AND/OR 99300-78-4

43 Levocetirizine Dihydrochloride AND/OR 130018-77-8

44 Pregabalin AND/OR 148553-50-8

45 Veratric Acid AND/OR 93-07-2

46 Fluconazole AND/OR 86386-73-4

47 Itraconazole AND/OR 84625-61-6

3.0

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SR.


QUANTITY

MT / MONTH

48 Cetirizine Dihydrochloride AND/OR 83881-51-0

49 Rabeprazole sodium AND/OR 117976-90-6

50 Pranlukast AND/OR 103177-37-3

51 Zonisamide AND/OR 68291-97-4

52 Telmisartan AND/OR 144701-48-4

53 Rosuvastatine calcium AND/OR 147098-20-2

54 Posaconazole AND/OR 1712228-49-2

55 Ursodiol AND/OR 128-13-2

TOTAL QUANTITY PRODUCTION PER MONTH 15

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LIST OF RAW MATERIAL

Product Name Raw Material Name KG/KG KG/MONTH

Group – I

isopropyl alcohol Hcl 0.92 1840.00

Ranney nickel (10%

charcoal)

0.12 240.00

Anhydrous aluminum

chloride

0.06 120.00

Ethyl acetate 2.33 4660.00

Hydrochloric acid 0.29 580.00

Hydrogen gas 0.01 20.00

Hyflowsuper cell 0.01 20.00

Isopropyl alcohol 14.17 28340.00

Liquid bromine 0.68 1360.00

Methanol 8.33 16660.00

M-hydroxy acetophenone 1.17 2340.00

N-methyl benzyl amine 0.86 1720.00

Phenylephrine hcl

Toluene 2.33 4660.00

Quinolic Acid 1.25 2500.00

N-methyl Piperazine 0.90 1800.00

Butanol 1.00 2000.00

Acetic Acid 0.30 600.00

Ofloxacin

Liquid Ammonia 0.45 900.00

Methyl piperazinyl 1.07 2140.00

4-chloro 2-methyl 10h-

thieno [2,3b][1,5]

benzodiazepine

1.33 2660.00

N N Dimethyl amine 5.33 10660.00

Olanzapine

Acetonitrile 4.00 8000.00

5-Chloro Aniline 2-4

Disulfonamide

1.20 2400.00

Sulphuric acid 0.16 320.00

Methanol 0.39 780.00

Formaldehyde 0.10 200.00

Sodium hydroxide 0.05 100.00


Hydrochlorothiazide

Activated carbon 0.01 20.00

5H-Dibenz [b,f]azepine-5-

carbonitrile

1.35 2700.00

Sodium nitrite 0.68 1360.00

Acetic acid 1.95 3900.00

Iron 0.08 160.00

Boron TriFluoride 0.35 700.00

Oxcarbazepine

IsoPropylAmine 2.25 4500.00

10-Methoxy-5H-

dibenz[b,f]azepine-5-


carbonitrile 1.23

2460.00

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Sodium nitrite 0.62 1240.00 carbonylchloride, 10-

Methoxyiminostilbene-5-

carbonylchloride

Acetic acid

1.70

3400.00

2,6 Dichlorophenol 0.62 1240.00

Sodium Methoxide

soln.25%

1.46 2920.00

Ethyl Chloro Acetate 0.44 880.00

Aniline 0.34 680.00

Caustic Lye 0.22 440.00

Chloro Acetyl Chloride 0.58 1160.00

Ethoxy ethanol 2.20 4400.00

Aluminum Chloride 0.66 1320.00

Sodium Hydroxide 0.30 600.00

Diclofenac sodium

Activated Carbon 0.01 20.00


Sodium Methoxide soln.25% 1.82 3640.00


Aniline 0.42 840.00

2,6 – dichloro diphenyl amine

(dcdpa)





Aniline 0.34 680.00



N-chloroacetyl-n-phenyl-2,6-

dichloro aniline (cpdca)





Aniline 0.33 660.00




Indolenone

Aluminium Chloride 0.66 1320.00

2,3 Lutidine 0.51 255.00


Hydrogen peroxide 0.37 185.00

Nitric acid 0.33 165.00

Sulfuric acid 1.2 600.00

3-Methoxy-1-propanol

Acetic anhydride

0.44 220.00


Toluene 10.55 5275.00

Dimethyl Sulphoxide 2.22 1110.00

Acetic anhydride 1.67 835.00

2-Hydroxymethyl-3-methyl-4-

(3-methoxy

propanoxyl)pyridine HCL


of 177


4Hydroxy Coumarin 0.92 460.00

Hydroxylamine hydrochloride 1.37 685.00

Potassium acetate 1.93 965.00


Methylene Dichloride 2.29 1145.00

1,2-benisoxazole-3-acetica acid

Hydrochloric Acid 0.47 235.00

Cis-BromoBenzoate 1.30 3250.00

Imidazole 1.16 2900.00

Dimethylformemide(DMF) 0.06 150.00

Toluene 3.80 9500.00

Sodium Bicarbonate 0.25 625.00


Hydro chloric acid 0.28 700.00

Ethyl Acetate 2.85 7125.00


Vacuum Salt 0.01 25.00

Methylene chloride 5.36 13400.00

P-Toluene Sulfonyl Chloride 0.78 1950.00

Sodium Carbonate 0.52 1300.00

Cis-tosylate

Methanol 2.37 5925.00

(2R-trans)-5-(4-

Fluorophenyl)-2-(1-

Methyl)-N,4diphenyl-1-[2-

Tetra hydroxy-4-hydroxy-

6-Oxo-2H-pyran-2yl)ethyl]-

1H-pyrrole-3-carboxamide

1.91 4775.00

Isopropyl Amine 3.98 9950.00


Atorvastatin calcium

Calcium Acetate solution 1.40 3500.00

(2R-trans)-5-(4- Fluorophenyl)

2-(1-

Methyl)-N,4diphenyl-1-[2-

Tetra

hydroxy-4-hydroxy- 6-Oxo-2H

pyran-2-

yl)ethyl]- 1H-pyrrole-3-

carboxamide

1.90 4750.00

Iso Propyl Alcohol 2.23 5575.00


tert-Butyl (4R,6R)-2-[[[6-(2-4-

fluorophenyl)-5-isopropyl-3-

phenyl-4-

(phenylcarbamoyl)pyrrol-1-

yl]ethyl]-2,2-dimethyl-1,3-

dioxan-4-yl]acetate

Calcium Acetate solution 1.39 3475.00

Benzopyran-2-

Carboxaldehyde Derivative

1.40 3500.00

Trimethylsulfoxonium

iodide

1.15 2875.00

Potassium hydroxide 0.56 1400.00

Nebivolol Hydrochloride

Benzyl amine 0.40 1000.00

of 177

Toluene 3.00 7500.00

Ammonium formate 0.60 1500.00


Methanol 5.20 13000.00

10% Sodium Hypochlorite 2.79 6975.00

Acetone 6.23 15575.00

Diflouro methoxy-2-MB 0.73 1825.00

Iso Propyl Acetate 11.54 28850.00


Pantoprazole chloro

compound

0.77 1925.00

Pantaprazol Sodium

Pantoprazole sulfide 1.15 2875.00

Pantoprazole chloro compound0.67 1675.00

Diflouro Methoxy-2-MB 0.64 1600.00


5-(Difluoromethoxy)-2- {[(

3,4Dimethoxypyridin - 2-yl)

methyl]thio}-1H-

benzimidazolee Iso propyl alcohol 4.02 10050.00

1,3-Dichloro acetone 0.63 1575.00

Guanylthiourea 0.56 1400.00

Potassium Iodide 0.02 50.00

N-((4-Chloromethyl)-2-

Thiozolyl)Guanidine

Hydrochloride

Acetone 1.91 4775.00

Methyl aceto acetate 1.14 3990.00 Methyl 3-amino-2 butenoate

Liq ammonia 2.75 9625.00

1,3-Difluorobenzene 0.55 1925.00


Methylene Chloride 3.25 11375.00

Chloroacetyl chloride 0.57 1995.00

4-Amino-1,2,4-Triazole 0.44 1540.00



Sodium Nitrite 0.32 1120.00


Ammonia Solution 0.55 1925.00

2,4-Difluoro-2-(1h- 1,2,4-

Triazole-1-Yl) Acetophenone

(Dfta)

Sodium bicarbonate 0.04 140.00

Cis-Bromobenzoate 1.10 3850.00

1H,1,2,4-Triazole 0.70 2450.00

Potassium carbonate 1.05 3675.00

Dimethyl formamide 1.85 6475.00


Toluene 1.56 5460.00

Triethyl amine 0.40 1400.00

Methane sulfonyl chloride 0.38 1330.00


cis-2-(2,4-Dichlorophenyl)-2-

(1H-1,2,4-triazol-1-ylmethyl)-

1,3-dioxolan-4-ylmethyl

methane sulphonate


1-(4-Methyxy) piperadine 0.66 2310.00

Paranitrochlorobenzene 0.54 1890.00

1-(4-Methoxyphenyl)-4-(4-

nitrophenyl) piperazine


of 177


Methanol 1.53 5355.00

Acetone 1.55 5425.00

Carbon 0.01 35.00

4- (2- Methoxyethyl) Phenol 0.80

2800.00

Epichlorohydrine 0.80 2800.00

2-[[4-(2-

Methoxyethyl)phenoxy]methyl-

oxirane Sodium hydroxide 0.24 840.00

4-(4-phenylbutoxy)benzoic acid0.80 2800.00

1-(3-amino-2-hydroxyphenyl)

Ethanone

0.46 1610.00

Methylene Dichloride(F/R) 4.70 16450.00

Dimethyl Formamide 0.04 140.00

Thionyl Chloride 0.47 1645.00

Pyridine 0.71 2485.00


3''-acetyl-2''-hydroxy-4-(4

phenylbutoxy) benzanilide


2-Bromo-1-cyclopropyl-2-

(2 flourophenyl)ethanone

0.88 2200.00

5,6,7,7a-tetrahydrothieno

[3,2-c]pyridine-2-(4H)-one

0.54 1350.00

Potassium Hydroxide 0.22 550.00

Methanol 8.76 21900.00


Methyl ethyl ketone 2.94 7350.00


Prasugrel Hydrochloride

Acetone 3.12 7800.00

2-Bromo-1-cyclopropyl-2-(2-

flourophenyl)ethanone

0.90 2250.00

5,6,7,7a-tetrahydrothieno[3,2

c]pyridine-2-(4H)-one

0.55 1375.00


5-[2-Cyclopropyl-1-(2-

fluorophenyl)-2-oxoethyl] -

5,6,7,7a-tetrahydrothieno[3,2-

c]pyridin-2(4H)-one

Methanol 2.70 6750.00

3-[(1-Methyl-2-{[4-(5-oxo-

4,5-dihydro-

[1,2,4]oxadiazol-3-yl)-

phenylamino]-methyl)-1H

benzoimidazole-

5carbonyl)-pyridin-2-

ylamino]- propionic acid

ethyl ester

0.97 2425.00

P-toluene sulphonic acid 0.25 625.00


Ethanol 25.00 62500.00

Hexachloroformate 0.28 700.00

Acetone 12.00 30000.00

Dabigatran


of 177


1,3-Dichloro acetone 0.53 1325.00

Guanylthiourea 0.50 1250.00

Potassium Iodide 0.02 50.00

Acetone 1.70 4250.00

Thiurea 0.25 625.00


N-Sulfamyl-3-chloro

propionamidineHCl

0.74 1850.00


Methanol 34.36 85900.00

Ammonia (23%) 0.24 600.00

Femotidine


L-Valine 0.50 1250.00


Methanol 8.89 22225.00

Toluene 12.22 30550.00

4-Bromomethyl-biphenyl-2-carbonitrile 0.91

2275.00

N-[(2'-Cyano[1,1'-biphenyl]-4-

yl)methyl]-L valine methyl ester



Benzene Sulfonic Acid 0.64 2240.00


Ethyl Chloroaceto acetate 0.55 1925.00


Haxene 0.22 770.00

Liq. Ammonia 0.96 3360.00


Methyl aceto acetate 0.50 1750.00

Mono Methyl Amine 3.75 13125.00

Monoethanol amine 0.45 1575.00

Ortho Chlorobenzaldehyde 0.40 1400.00

Phthalic anhydride 1.00 3500.00

Piperidine 0.02 70.00

Sodium chloride 0.50 1750.00

Sodium hydride 0.28 980.00

Amlodipinbesylate

Toluene 0.23 805.00


Mono ethanol amine 0.45 1575.00

Toluene 9.11 31885.00







Amlodipine base


of 177


Hexane 1.91 6685.00



Hexane 35.6 124600.00

Mono Methyl Amine 37.5 131250.00





Methanol 2.60 9100.00

Acetone 2.63 9205.00

Carbon 0.02 70.00

Palladium carbon 0.01 35.00


Phenyl chloroformate 1.01 3535.00



Hydragin hydrate 0.84 2940.00

n-Butanol 1.88 6580.00

Formamidine acetate 0.82 2870.00

2-Bromo butane 1.60 5600.00


Hydrobromic acid 12.32 43120.00

2,4-dihydro-4-[(4-(4-

hydroxyphenyl)-1-

piperazinyl)phenyl]-2-(1-

methylpropyl)-3h-1,2,4-triazole-

3-one

Sodium carbonate 1.12 3920.00

4- (2- Methoxyethyl)

Phenol

0.89 3115.00



Mono isopropyl amine 2.68 9380.00

Toluene 3.57 12495.00


Caustic lye 0.27 945.00


Tartaric Acid 0.24 840.00

Metoprolol tartrate

Methanol 0.63 2205.00

4- (2- Methoxyethyl) Phenol 0.67

2345.00




Toluene 2.69 9415.00


1-(Isopropylamino)-3-[4-(2-

methoxyethyl) phenoxy]-2-

propanol


4- (2-Methoxyethyl) Phenol 0.89 3115.00


Metoprolol succinate


of 177


Toluene 3.57 12495.00




Succinic Acid 0.19 665.00

Methanol 0.63 2205.00

Cis-BromoBenzoate 1.53 3825.00

Imidazole 1.36 3400.00

Dimethylformemide(DMF) 0.07 175.00

Toluene 4.46 11150.00





Vacuum Salt 0.01 25.00

PeraHydroxy phenyl n-

acetyl piperazine

0.56 1400.00

Dimethyl Sulfoxide 1.66 4150.00

Sodium methoxide powder 0.14 350.00

Acetone 0.67 1675.00

Methanol 0.92 2300.00

Ketoconazole



Mono ethanol amine 0.30 1050.00

Toluene 6.07 21245.00




Hydrochloric Acidl 0.03 105.00





Hexane 1.28 4480.00



Phthaloyl amlodipine

Hexane 2.38 8330.00





Methanol 2.19 7665.00

Acetone 2.22 7770.00

Carbon 0.02 70.00

2,4-Dihydro-4-[4-[4-(4-

methoxyphenyl)-1-

piperazinyl]phenyl]-2-(1-

methylpropyl)-3H-1,2,4-triazol-

3-one


of 177






n-Butanol 1.59 5565.00





Acetone 10.67 26675.00


Di isopropyl ethylamine 0.04 100.00


Methylene Dichloride

(MDC)

12.00 30000.00


Methanol 14.80 37000.00

N-vinyl pyrolidone 0.72 1800.00



Tertiary Butyl amine 0.20 500.00

Thiol Acetic acid 0.49 1225.00

Thiophene-2-ethylamine 2.32 5800.00

Montelukast sodium

Toluene 48.00 120000.00

L-Valine 0.45 1125.00


Methanol 8.00 20000.00

Toluene 25.00 62500.00

4-Bromomethyl-biphenyl-

2-carbonitrile

0.82 2050.00


Valeryl Chloride 0.34 850.00

Tri Ethyl Amine 0.20 500.00

Sodium Azide 0.16 400.00


Sodium Sulphate 0.10 250.00

Tri Butyl tin Chloride 0.80 2000.00

Hydrogen Gas 0.01 25.00


Xylene 2.40 6000.00



N-Hexane 2.00 5000.00

Valsartan


Venlafaxine Hydrochloride 4-Methoxy Benzoyl Cyanide 0.97 2425.00

of 177

Methanol 3.50 8750.00

Sodium Methoxide 0.91 2275.00

Cyclohexanone 0.90 2250.00

Toluene 4.81 12025.00


Tetra butyl ammonium

bromide

0.05 125.00


formic soda 1.94 4850.00

Formaldehyde 1.12 2800.00





Hyflowsupercell 0.04 100.00

IsoPropylAlcohol 14.6 36500.00

IsoPropyl Alcohol HCl 1.09 2725.00

Activated Charcoal 0.01 25.00

1-[((4

Chlorophenyl)phenyl)methyl]

-4-

[(phenylsulphonyl)]piperazine

0.92 22300.00

2(2-Chloroethoxy )acetamide 0.29 725.00

4-Hydroxy benzoic acid 0.32 800.00





Potassium iodide 0.03 75.00

Toluene 30.30 75750.00


Acetone 9.30 23250.00

LevocetirizineDihydrochloride



R-(-)-3- (Carbamoyl

methyl)-5-methyl hexanoic

acid

1.37 3425.00

Liquid Bromine 1.23 3075.00

Hyflosupercell 0.07 175.00



Pregabalin


Catechol 0.92 2300.00


Dimethyl Sulphate 2.30 5750.00

Veratric Acid


of 177

Acetyl Chloride 1.04 2600.00



Sodium Hypo Chlorite 12.30 30750.00


Sodium meta bi sulphate 0.07 175.00


1,2,4-Triazole 0.66 2310.00

1,3-Diflurobenzene 0.80 2800.00

4-amino-1,2,4-Triazole 0.65 2275.00

Aluminum Chloride 0.96 3360.00

Ammonia Solution 3.36 11760.00


Chloroacetyl Chloride 0.84 2940.00

Citric acid 0.06 210.00



IsoPropylAlcohol 3.16 11060.00

Methylene Chloride 4.80 16800.00



Sodium Nitrite 0.47 1645.00

Toluene 8.40 29400.00

Fluconazole

Trimethylsulphoxonium

iodide

1.32 4620.00

1-(4-MethyxyPhenyl)

piperazine

1.02 3570.00

1H,1,2,4-Triazole 0.83 2905.00


Acetone 0.06 210.00


Cis-Bromobenzoate 1.31 4585.00










Methanol 0.30 1050.00


n-Butanol 0.03 105.00


Itraconazole


of 177







Toluene 0.11 385.00


4-Chloro

benzhydrylpiperazine

0.92 3220.00

Toluene 8.20 28700.00

2-Chloroethanol 0.46 1610.00

Triethylamine 1.00 3500.00


Sodium monochloro acetate 0.70 2450.00


Dimethylformamide 0.20 700.00

Methylene dichloride 3.00 10500.00

Acetone 3.00 10500.00

Hydrogen chloride 0.52 1820.00

Cetirizine Dihydrochloride


2,3 Lutidine 0.46 230.00


Hydrogen peroxide 0.33 165.00

Nitric acid 0.30 150.00

Sulfuric acid 1.08 540.00

3-Methoxy-1 -propanol

Acetic anhydride

0.40 200.00


Toluene 13.5 6750.00

Dimethyl Sulphoxide 2.00 1000.00



Thionyl chloride 0.53 265.00

Sodium sulphate 0.10 50.00


2-mercapto benzimidazole 0.53 265.00

Sodium hypochlorite (8%) 3.27 1635.00

Acetone 1.50 750.00

Sodium Hydro Sulphate 0.12 60.00

Mono Methyl Amine in

Methanol

0.10 50.00

Isopropyl Alcohol 3.00 1500.00

Rabeprazole sodium


Pranklukast 4-(4-phenylbutoxy) benzoic

acid 1.00 3500.00

of 177


ethanone 0.58 2030.00


Dimethyl Formamide 0.05 175.00


Pyridine 0.90 3150.00



Sulfuric Acid 5.00 17500.00



4HydroxyCoumarin 1.56 780.00

Hydroxylamine hydrochloride 2.34 1170.00

Potassium acetate 3.30 1650.00




Ethylene dichloride 6.85 3425.00

1,4 Dioxane 0.78 390.00

Chlorosulfonic acid 0.96 480.00


Toluene 2.40 1200.00

Phosphorus Oxychloride 0.16 80.00

Ammonia Gas 1.04 520.00

Ethyl Acelate 11.56 5780.00


Zonisamide


Acetone 1.34 3350.00



Bibenzimidazole 0.85 2125.00

Bromo methyl ester 0.85 2125.00

Celite 0.04 100.00


Methanol 29.38 73450.00



Telmisartan

Recoveries (-) Acetone 1.27 3175.00

4-Fluoro benzaldehyde 0.52 260.00

4-Methyl-3-oxo-pentanoic

acid ethyl ester

0.66 330.00


Methyl Iodide 0.60 300.00

Methanol 5.50 2750.00

S-Methyl isothio urea 0.35 175.00

Rosuvastatine calcium

2,3-Dichloro-5,6-dicyano 0.85 425.00

of 177

benzoquinone

Hexamethylphosphoramide 1.00 500.00


Meta chloroperoxy benzoic

acid

1.19 595.00

Methyl amine 0.10 50.00

Ethanol 2.50 1250.00


Sodium hydride (60%) 0.01 5.00

Di methoxy ethane 3.00 1500.00


Diisobutylaluminium hydride 0.01 5.00

Toluene 8.00 4000.00

Methyl(3R)-3-(tert butyl di

methyl silyloxy)-5-oxo-6- tri

phenyl

phosphoranylidenehexanoate

1.45 725.00


N,N-Dimethyl formamide 3.00 1500.00

Hydrogen fluoride 0.05 25.00

Tetra Hydro Furan 2.50 1250.00


Diethyl methoxyborane 0.20 100.00

Sodium boro hydride 0.01 5.00

Calcium chloride 0.13 65.00

4-Hydroxyphenyl-

piperazinyltriazolone

1.40 2100.00

(5R,Cis)-toluene-4-sulfonic

acid-5-(2,4-difluorophenyl)-5-

(1H-1,2,4-triazol-1-yl)methyl

tetrahydrofuran-3-yl

methylester

1.40 2100.00



Sodium Chloride 1.40 2100.00


Dimethyl Sulfoxide 11.00 16500.00

Isopropyl Alcohol 83.00 1124500.00


Methanol 23.00 34500.00

Acetone 19.00 28500.00

Palladium Carbon 0.90 1350.00

Posaconazole


Chenodeoxycholic acid 2.75 4125.00

Acetone 90.70 136050.00

N-Bromosuccinamide 2.24 3360.00

Ursodiol

Potassium tertbutoxide 2.44 3360.00

of 177

Ranney Nickel 0.96 1440.00


Isopropyl alcohol 34.20 51300.00


Triethylamine 0.55 825.00

of 177

ANNEXURE - III

___________________________________________________________________________

BRIEF MANUFACTURING PROCESS DESCRIPTION

Group – I

1. Phenylephrine HCl

Process Description:

M-hydroxyacetophenone reacts with bromine in presence of aluminium chloride to form M-

hydroxyl bromoacetophenone which will react with N-methyl benzyl amine in presence of

Ranney Nickel to obtain phenylephrine hydrochloride.

Route of Synthesis:

of 177

Material Balance:

Stage-I

Input QTY.(kgs) Output QTY.(kgs) m-hydroxyacetophenone 350 Stage- I Mass 500 Ethyl acetate 700 HBr 210

An.Aluminium chloride 17.5 Solvent Liq. Bromine 204 Toluene recovery 665 Toluene 700 Toluene loss 21 n-methyl benzyl amine 258 Ethyl acetate recovery 665 Water 250 Ethyl acetate loss 21

Acidic isopropyl alcohol 75 Liquid waste

Water 250

Aluminum chloride 17.5

Toluene 14

Ethyl acetate 14

Acidic Isopropyl alcohol 75

Solid waste 0

Gaseous waste 0

Organic residue 102 Total 2554.5 Total 2554.5

Stage-II

Input QTY.(kgs) Output QTY.(kgs) Stage- I Mass 500 Stage- II mass 400

Methanol 2500 Solvent Ranney nickel (10% charcoal) 25 Methyl recovery 2250 Hydrogen gas 2 Methyl loss 125

Hyflow powder 2 Liquid waste Water 250 Water 250

Methanol 63

Organic 92

Solid waste 99

Gaseous waste 0


Stage-III

Input QTY.(kgs) Output QTY.(kgs) Stage- II Mass 400 Stage- III Mass 375

Isopropyl alcohol 2000 Solvent HCl 88 Isopropyl alcohol recovery 1800 water 250 Isopropyl alcohol loss 100

Acidic isopropyl alcohol 200 Liquid waste

Water 250

Isopropyl alcohol 100

Acidic isopropyl alcohol 200

Solid waste 113

Gaseous waste 0

of 177


Stage-IV

Input QTY.(kgs) Output QTY.(kgs)

Stage- III Mass 375 Phenylephrine HCL -Product 300

Isopropyl alcohol 2250 Solvent Activated charcoal 12 Isopropyl alcohol recovery 1800 Hyflow powder 2 Isopropyl alcohol loss 112.5

Liquid waste 0

Solid waste 351.5

Gaseous waste 0


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2. Ofloxacin Process Description:

Quonalinic acid & N- methyl piperizine reacted in butanol. The reaction mass acetic acid is

added mass is neutralized to give ofloxacin. Purified, filtered & dried to give ofloxacin.

Route of Synthesis:

Material Balance:

Stage-I

Input QTY.(kgs) Output QTY.(kgs) Quinolic Acid 125.00 Ofloxacin 100.00 N-methyl Piperazine 90.00 Butanol Rec 95.00 Butanol 100.00 Dry loss 20.00 Acetic Acid 30.00 Solvent Loss 05.00 Liq Ammonia 45.00 Aqu effluent 170.00 Total 390.00 Total 390.00

of 177

3. Olanzapine


Charge Methyl piperazinylChloro-thieno benzodiazepine, N N DMA, catalyst heat and reflux distilled out. Add Acetonitrile cool & filters dry in RCVD to get Olanzapine.

Route of Synthesis:

Material Balance:

Stage-I


Methyl piperazinyl 80.00 Olanzapine 75.00 Chloro-thieno benzodiazepine 100.00 Aqu. Effluent 280.00 N N DMA 400.00 Process loss 25.00 Catalyst 10.00 Solvent Recovery 510.00

Acetonitrile 300.00

Total 890.00 Total 890.00

of 177

4. Hydrochlorothiazide

Process description:

5-Chloro Aniline 2-4 Disulphonamide in water reacted with Formaldehyde at 80°C gives

Hydrochlorothiazide. Centrifuge the reaction mass, Give charcoal treatment and filter, dry

the material.

Route of Synthesis:

Material balance:

Stage-I

INPUT QTY.(KGS) OUTPUT QTY.(KGS)

5-Chloro Aniline 2-4 Disulphonamide 240 Hydrochlorothiazide 200

Sulphuric acid 32.2 Activated carbon 3.5

Methanol 79.2 Effluent 570.5

Formaldehyde 20.4

Sodium hydroxide 10

Hydrochloric acid 28.7

Activated carbon 3.5

Purified water 360

Total 774 Total 774

of 177

5. Oxcabazepine


5H-Dibenz[b,f]azepine-5- carbonitrile ; Sodium nitrite treated in presence of Acetic acid &

Iron Boron Trifluoride is added. The mass is filtered to give crude product, crystallized from

IPA, filtered & dried to give Oxcabazepine.

Route of Synthesis:

of 177

Material balance:

Stage-I Input QTY.(kgs) Output QTY.(kgs) 5H-Dibenz [b,f]azepine-5- carbonitrile 135.00 Stage-1 109.00 Sodium nitrite 68.00 Aqu. Effluent for Sodium nitrite 279.00

Acetic acid 185.00 Total 388.00 Total 388.00

Stage-II

Input QTY.(kgs) Output QTY.(kgs) Stage -1 109.00 Stage-1 87.00

Iron 8.00 Aqu. Effluent for Fe Acetate 175.00

Acetic acid 110.00

Boron TriFluoride 35.00


Stage-III

Input QTY.(kgs) Output QTY.(kgs) Stage -2 87.00 Oxcabazepine 100.00 IPA 225.00 IPA Rec 202.00

Dry Loss 10.00 Total 312.00 Total 312.00

of 177

6. 10-Methoxy-5H-dibenz[b,f]azepine-5-carbonylchloride, 10-

Methoxyiminostilbene-5-carbonylchloride


5H-Dibenz[b,f]azepine-5- carbonitrile ; Sodium nitrite treated in presence of Acetic acid &

Iron Boron Trifluoride is added. The mass is filtered to give crude product, crystallized from

IPA, filtered & dried to give Oxcabazepine.

Flow Chart:

Material balance:

Stage-I Input QTY.(kgs) Output QTY.(kgs) 5H-Dibenz [b,f]azepine-5- carbonitrile 135.00 Stage-1 109.00 Sodium nitrite 68.00 Aqu. Effluent for Sodium nitrite 279.00

Acetic acid 185.00 Total 388.00 Total 388.00


carbonitrile

Sodium nitrite

Acetic acid

Iron

Acetic acid

Boron Trifluoride

Stage-1

10-Methoxy-5H-dibenz [b,f]azepine-5-

carbonylchloride, 10-Methoxyiminostilbene-5-

carbonylchloride

of 177

7. Diclofenac Sodium


Stage-I:

2,6 DCP, sodium methoxide, ethyl chloro acetate, aniline caustic are added to reactor

inrequiredproportion.The mass is allowed to react together at required temperature and

pressure condition, once the reaction is over, the material is filtered and dried in drier and

packed in drums and stored as DCDPA

Stage-II:

DCDPA, ethoxy ethanol, chloro acetyl chloride are added to a reaction vessel,

hydrogenchloride gas generated during the reaction is scrubbed off with the help of caustic

solution in scrubber tower. The material filtered, washed and dried packed and store as

CPDCA

Stage-III:

CPDCA, aluminium chloride to allow react in a reactor and controlled temperature

condition.The mass is then quenched in water and filtered, hydrogen chloride gas generated

during reaction and quenching is taken to scrubber system. Neutralized material is filtered,

washed, dried, packed and store as Indolinone

Stage-IV:

Indolinone, caustic and solvent added reaction vessel, reaction is done under

controlledcondition the material after reaction is over, filtered, and dried packed and stored

as DFS.

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Material balance:

Stage-I

Input QTY.(kgs) Output QTY.(kgs) 2,6 D.C.P 61.76 D.C.D.P.A 80.00 Sodium Methoxide soln.25% 145.60 Solvent Reco 184.00 Ethyl Chloro Acetate 43.52 NaCl 19.20

Aniline 33.92 Effluent 113.60 Caustic Lye 22.00 Process loss 32.80

Water 122.80


Stage-II

Input QTY.(kgs) Output QTY.(kgs) D.C.D.P.A 80.00 C.P.D.C.A 100.00 Chloro Acetyl Chloride 58.00 HCL gas 15.00

Ethoxy ethanol 220.00 Solvent Reco 235.00


Stage-III

Input QTY.(kgs) Output QTY.(kgs) C.P.D.C.A 112.00 Indolinone 100.00 Aluminium Chloride 65.60 Aqu Effluent 110.00 Water 83.00 HCL 15.00

Drying Loss 35.60


Stage-IV

Input QTY.(kgs) Output QTY.(kgs) Idolinone 109.00 Diclofenac Sodium 100.00 Sodium Hydroxide 30.20 Effluent 69.00 Water 60.00 Charcoal 1.00

Charcoal 0.8 Dry Loss 30.00 Total 200.00 Total 200.00

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8. 2,6 – dichloro diphenyl amine (dcdpa)





packed in drums and stored as DCDPA.

Route of Synthesis:

Material balance:

Stage-I



Water 192.80


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9. N-chloroacetyl-n-phenyl-2,6-dichloro aniline (cpdca) Process Description:

Stage-I:





Stage-II:




CPDCA.

Route of synthesis:

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Material balance:

Stage-I



Water 192.80


Stage-II




of 177

10. Indolenone


Stage-I:





Stage-II:




CPDCA.

Stage-III:

CPDCA, aluminium chloride to allow react in a reactor and controlled temperature

condition.The mass is then quenched in water and filtered, hydrogen chloride gas generated

during reaction and quenching is taken to scrubber system. Neutralized material is filtered,

washed, dried, packed and store as IndolinoneDiclofenac Sodium (DFS).

Route of Synthesis:

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Material Balance:

Stage-I



Water 192.80


Stage-II




Stage-III

Input QTY.(kgs) Output QTY.(kgs) C.P.D.C.A 112.00 Indolinone 100.00 Aluminium Chloride 65.60 Aqu Effluent 150.00 Water 123.00 HCL 15.00

Drying Loss 35.60


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11. 2-Hydroxymethyl-3-methyl-4-(3-methoxy propanoxyl) pyridine HCL


Stage-1 :

2, 3-Lutidine is reacted with Hydrogen Peroxide in presence of Acetic Acid to give N- Oxide

it further reacts with Nitration mixture (Nitric Acid + Sulfuric Acid) to give Stage-1.

Stage-2:

Stage-1 is reacted with 3-Methoxy-1-Propanol and Sodium Hydroxide to get Stage-2

Compound

Stage-3:

Stage-2 Compound is reacted with Acetic Anhydride, Sodium Hydroxide and Hydrochloric

Acid to get Stage-3 Compound.

Route of Synthesis:

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Mass Balance:

STAGE-1


2,3 Lutidine 46.00 Stage-1 65.00

Acetic acid 46.00 Spent acid 140.00

Hydrogen peroxide 33.00 Effluent 200.80

Nitric acid 30.00 Organic Residue 7.20

Sulfuric acid 108.00

Water 150.00


STAGE-2


Stage-1 65.00 Stage-2 80.00

3-Methoxy-1 –propanol

Acetic anhydride

40.00 Toluene Reco 235.00

Sodium hydroxide 18.50 DMSO Reco 188.00

Toluene 250.00 Solvent loss 22.00

DMSO 200.00 Inorganic solid waste 29.70

Organic waste 11.80

Water generate 7.00


STAGE-3


Stage-2 80.00 Stage-3 90.00

Acetic anhydride 150.00 Toluene Reco 660.00

NaOH 20.00 Acetic anhydride Reco 107.00

HCL 20.00 Effluent 160.50

Toluene 700.00 Organic Residue 13.50

Water 100.00 Process loss 39.00

Total 1070.00 Total 1070.00

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12. 1,2-benisoxazole-3-acetica acid


Stage-I:

4-Hydroxycoumarin was reacted with hydroxylamine HCl in presence of potassium acetate

anhydrous in methanol at desired temperature and appropriate condition.

Route of Synthesis:

Mass Balance:

STAGE-I


Methanol 153.00 Stage-1 214.00

4Hydroxy Coumarin 195.30 Methanol Reco 137.7

Hydroxylamine hydrochloride 293.00 Methanol loss 15.3

Potassium acetate 413.00 Effluent 838.30

Sodium hydroxide 20.00 Dry loss 30.00

Methylene Dichloride 290.00 Organic Residue 29.00

Hydrochloric Acid 100.00

Water 300.00

Total 1264.30 Total 1264.30

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13. Cis-tosylate Process Description: Stage I:

CBB is reacted with IMD in the presence of DMF as solvent. The reaction mass is quenched in sodium bicarbonate solution and the product is extracted with toluene. The aqueous layer is kept for IMD recovery. The organic layer containing the product is reacted with sodium hydroxide solution. After completion of reaction, the pH of the mass is adjusted with hydrochloric acid. mass is diluted with water and centrifuged. The wet cake is dissolved in ethyl acetate and treated with carbon. The mass is filtered and the ethyl acetate is distilled off. The residue is cooled and centrifuged. The mass is dried to produce KT-I.

Stage II:

KT-I is reacted with PTSC in the presence of sodium carbonate and methylene chloride as

solvent. The reaction mass is diluted and the organic layer separated. Methylene chloride is

distilled off completely from the organic layer and the residue is diluted with methanol and

water. The mass is centrifuges and washed with methanol and water mixture. The mass is

dried to produce Cis-Tosylate (KT-II).

Route of Synthesis:

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Material Balance:

Stage-I


CBB 780 Stage-1 450

IMD 693.3 IMD Rec 360

DMF 37.2 Toluene Rec 2207.0

Toluene 2275.5 Ethyle Acetate 1620.0

Sodium Bicarbonate 148.2 Aq. Effluent 1599.4

Sodium hydroxide 120.0 Spent carbon 12.0

Water 705.0 Residue 130.0

HCl 156 Process loss 254.9

Ethyl Acetate 1706.4

Activated Carbon 6.0

Vacuum Salt 6.0


Stage-II


Stage-1 450.0 Stage-2 600.0

Methylenechloride 3217.5 Methylenechloride Rec 3024.0

P-Toluene Sulfonyl Chloride 465.0 Methanol Rec 1375.0

Sodium Carbonate 307.5 Aq. Effluent 778.0

HCl 12.0 Process Loss 400

Methanol 1425.0

Water 420


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14. Atorvastatin Calcium Process Description: 2R-trans)-5-(4-Fluorophenyl)-2-(1-Methyl)-N,4diphenyl-1-[2-Tetra hydroxy- 4hydroxy-6-Oxo-

2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide treated with NaOH in IPA. The mass is

treated with calcium acetate solution. The crude obtained is crystallized from IPA to give

atorvastatin calcium.

Route of Synthesis:

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Material Balance:

Stage-I

Input QTY.(kgs) Output QTY.(kgs) Stage - 1 89.00 Aqu. Effluent for IPA Rec 358.00

(2R-trans)-5-(4- Fluorophenyl)-2-(1-

Methyl)-N,4diphenyl-1-[2- Tetra

hydroxy-4-hydroxy- 6-Oxo-2H-pyran-2-

yl)ethyl]- 1H-pyrrole-3-carboxamide 191.00

IPA 225.00

NaOH 31.00


Stage-II


Stage – 1 89.00 Stage-2 101.00

Calcium Acetate solution 140.00 Aqu. Effluent for Calcium 128.00

Acetate solution Rec


Stage-III


Stage – 2 101.00 Atorvastatin Calcium 100.00

IPA 173.00 Aqu. Effluent for IPA Rec 155.00

Dry Loss 19.00


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15. Tert-Butyl (4R,6R)-2-[[[6-(2-4-fluorophenyl)-5-isopropyl-3-phenyl-4-

(phenylcarbamoyl)pyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate Process Description:

2R-trans)-5-(4-Fluorophenyl)-2-(1-Methyl)-N,4diphenyl-1-[2-Tetra hydroxy- 4hydroxy-6-Oxo-

2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide treated with NaOH in IPA.

Route of Synthesis:

Material Balance:

Stage-I

Input QTY.(kgs) Output QTY.(kgs) Stage - 1 89.00 Aqu. Effluent for IPA Rec 358.00

(2R-trans)-5-(4- Fluorophenyl)-2-(1-

Methyl)-N,4diphenyl-1-[2- Tetra

hydroxy-4-hydroxy- 6-Oxo-2H-pyran-2-

yl)ethyl]- 1H-pyrrole-3-carboxamide 191.00

IPA 225.00

NaOH 31.00


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16. Nebivolol hydrochloride


Benzopyran-2-Carboxaldehyde Derivative treated with Trimethylsulfoxonium iodide In

presence of Potassium hydroxide & Water. The mass is further treated with Benzyl amine &

Toluene, Ammonium formate using Pd/Catalyst. The mass is crystallized from Methanol,

filtered & dried to give Nebivolol.

Route of Synthesis:

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Material Balance:

Stage-I

Input QTY.(kgs) Output QTY.(kgs) Benzopyran-2- CarboxaldehydeDerivative 140.00 Stage-1 81.00

Trimethylsulfoxonium iodide 115.00 Aqu. Effluent 430.00

Potassium hydroxide 56.00

Water 200.00


Stage-II

Input QTY.(kgs) Output QTY.(kgs) Stage-1 81.00 Stage-2 121.00 Benzyl amine 40.00 Toluene Rec 270.00 Toluene 300.00 Solvent Loss 30.00 Total 421.00 Total 421.00

Stage-III

Input QTY.(kgs) Output QTY.(kgs)Stage-2 121.00 Stage-3 168.00 Ammonium formate 60.00 Methanol Rec 108.00 Hydrogen gas 1.00 Solvent Loss 12.00 Methanol 120.00 Hydrogen gas 1.00

Process loss 13.00 Total 302.00 Total 302.00

Stage-IV

Input QTY.(kgs) Output QTY.(kgs)Stage-3 168.00 Nevivolol 100.00 Methanol 400.00 Methanol Rec 360.00

Solvent Loss 40.00

Dry loss 28.00

Carbon dioxide 40.00 Total 568.00 Total 568.00

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17. Pantaprazol Sodium Process Description:

Pantoprazole chloro compound will react with 5-difluoromethoxy-2-mercapto

benzamidazole in presence of Base in organic solvent to get PT-S compound. PT-S

compound will react with sodium hypochlorite in presence of organic solvent to get PT-1

compound. PT-1 compound will reacts with sodium hydroxide in presence of organic solvent

to get Pantoprazole sodium sesquihydrate.

Route of Synthesis:

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Material Balance:

Stage-1

Input QTY.(KGS) Output QTY.(kgs)

Pantoprazole chloro compound 77 Stage-1 115

Diflouro Methoxy-2-MB 73.5 IPA MLs 627

NaOH 30 Evaporation loss 15.1

R.O. water 200.50 Evaporation loss 8.4

IPA 462 Aq. layer 77.5

Total 843 Total 843

Stage-2


Stage-1 115 Stage-2 103.5

10% NaOCl 279 Evaporation loss 8

IPA 692 IPA MLs 885

R.O. water 186.5 Evaporation loss 4

Aq. layer 272


Stage-3


Stage-2 103.5 Pantoprazole Sodium- API 100

NaOH 11 Evaporation loss 10

Acetone 623 Evaporation loss 7

R.O. water 18 Acetone MLs 638.5


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18. 5-(Difluoromethoxy)-2- {[( 3,4Dimethoxypyridin - 2-yl) methyl]thio}-1H-

benzimidazole


Pantoprazole chloro compound will react with 5-difluoromethoxy-2-mercapto

benzamidazole in presence of Base in organic solvent to get PT-S compound. PT-S.

Route of Synthesis:

Material Balance:

Stage-1


Pantoprazole chloro compound 77 Stage-1 115

Diflouro Methoxy-2-MB 73.5 IPA MLs 627

NaOH 30 Evaporation loss 15.1

R.O. water 291.50 Evaporation loss 8.4

IPA 462 Aq. layer 168.5

Total 934 Total 934

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19. N-((4-Chloromethyl)-2-Thiozolyl) Guanidine Hydrochloride


Stage-1:

1, 3-Dichloro acetone reacts with Guanylthiourea in the presence of Acetone as solvent

media to give Stage-2 as product.

Route of Synthesis:

Material Balance:

Stage-1

Input Qty. Output Qty

1,3-Dichloro acetone 53.00 Stage-1 88.97

Guanylthiourea 50.00 Acetone Rec. 161.00

Potassium Iodide 2.40 Generated water 7.51

Acetone 170.00 Inorganic solid waste 2.40

Organic solid waste 7.52

Solvent Loss 8.0


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20. Methyl 3-amino-2 butenoate


STAGE –1A:

Charge Methyl acetoacetate and ammonia solution into the reactor and maintain for 6

hours. Filter the mass.

Route of Synthesis:

Material Balance:

Stage-1A

INPUT QTY.(KGS) OUTPUT QTY.(KGS) Methyl aceto acetate 40 Stage 1A 35 Liq ammonia 96 Aq. Effluent 111 Total 146 Total 146

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21. 2,4-Difluoro-2-(1h- 1,2,4-Triazole-1-Yl) Acetophenone (Dfta)


Stage-I:

Charge Methylene dichloride and aluminium chloride into the reactor. Cool the mass to

below 5°C. Charge 1,3-Difluorobenzene into the reactor. Add slowly chloroacetyl chloride

into the reactor for 4 to 5 hours below 10°C. Charge the reaction mass to ice and

hydrochloric acid. Stir the reaction mass for 4 hours and separate the layers. Distil off MDC

completely below 50°C. Charge isopropyl alcohol and 4-amino-1,2,4-triazole into the reactor

and maintain for 6 hours at 45-50°C. Cool the reaction mass to 10°C and centrifuge material

and dry to produce 2-(1H-1,2,4-triazole-1-yl)-2’,4’-difluoroacetophenone salt.

Route of Synthesis:

Material Balance:

Stage-I

Input QTY.(KGS) Output QTY.(KGS)

1,3-Difluorobenzene 200 Stage-I Compound 480 Aluminium Chloride 240 Sol Rec(MDC) 1050 Methylene Chloride 1200 Sol Rec (IPA) 740 Chloroacetyl chloride 210 AlCl3 gel for Rec. 1100 4-Amino-1,2,4-Triazole 162 Aq. Effluent 490 IPA 790 Residue 30 Sodium bicarbonate 15 Solvent loss 202

Hydrochloric acid 75

Ice & Water 1200 Total 4092 Total 4092

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22. cis-2-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-

ylmethyl methane sulphonate

Process Description: Stage-I:

charge dimethyl formamide, cis-2[bromomethyl-2-(2,4 dichlorophenyl)1,3 dioxalane-4-

yl)methyl benzoate and 1H-1,2,4 triazole into a reactor. Charge sodium hydroxide solution

into the reactor.Heat to reflux and maintain for 8 hours. After completion of reaction, cool

the mass below 35°C and charge potassium carbonate. Stir the mass for 30 minutes and

filter. Charge the filtrate and distil off DMF completely. Charge water and toluene into the

reactor and stir for 30 minutes. Discard the bottom aqueous layer to ETP. Cool the organic

layer to 10-15°C. Centrifuge the material and wash with toluene. Dry the material at 60-65°C

to produce Cis-[2- (2,4-dichlorophenyl)-2-(1H,1,2,4-triazol-1yl methyl)1,3 dioxolan-

4yl]methanol.

Stage-II:

Charge methylene dichloride, Step-I compound and triethyl amine into a reactor. Slowly add

methane sulfonyl chloride into the reactor at 10-15°C. After completion of the reaction,

charge water and stir for 30 minutes. Separate the layers. Charge organic layer in to the

reactor and charge carbon. Stir for 30 minutes and filter the mass into another reactor. Add

hydrochloric acid into the reactor at 25-30°C. Cool the mass to 10-15°C. Centrifuge and wash

with methylene dichloride. Dry the material at 45-50°C to produce Cis-[2-(2, 4 -

dichlorophenyl) - 2 - (1H,1, 2, 4 - triazol - 1yl- methyl) 1,3-dioxolan-4yl]-methyl methane

sulfonate (ITR-INT-A).

Route of Synthesis:

of 177

Mass Balance:

Stage-01 Int-A


Cis-Bromobenzoate 111.3 Triazole derivative 95.8

1H,1,2,4-Triazole 70.4 Solvent rec (DMF) 181.7

Potassium carbonate 105.7 Solvent rec (Tol) 153.3

Dimethyl formamide 186.7 Aq. Effluent 238.3

Sodium hydroxide 10.6 Residue 64.5


Water 100.7


Stage-02 Int-A


Triazole derivative 95.8 ITR-INT-A 101.5

Triethyl amine 40.2 Solvent rec (MDC) 187.0

Methane sulfonyl chloride 38.3 Aq. Effluent 92.0

Methylene chloride 193.8 Spent carbon 7.7

Activated Carbon 3.8 Residue 56.2

Sodium hydroxide 6.9 Solvent loss 6.8

Water 72.4


of 177

23. 1-(4-Methoxyphenyl)-1-(4-nitrophenyl) piperazine


Stage-I:

Charge dimethyl formamide, potassium carbonate and 1-(4-Methyxy) piperadine into a

reactor. Heat the mass to 60-65°C. Add paranitrochlorobenzene for 3-4 hours at same

temperature. After completion of the reaction distil off dimethyl formamide completely.

Cool the mass and charge methanol and carbon into the reaction. Maintain the mass for 30

min at 50-55°C and filter into another reactor. Cool the filtrate to 10-15°C and centrifuge.

Wash the material in water. Slurry wash the cake with acetone to produce 1-(4-

Methoxyphenyl)-1-(4-nitrophenyl) piperazine.

Route of Synthesis:

Mass Balance:

Stage-01


1-(4-Methyxy) piperadine 86.9 Stage-I 132.4

Paranitrochlorobenzene 71.2 Solvent Rec (Methanol) 198.9

Potassium carbonate 77.1 Solvent Rec (Acetone) 200.2

Dimethyl formamide 101.5 Solvent Rec (DMF) 98.1

Methanol 203.3 Aq. Effluent 176.5

Acetone 205.7 Spent carbon 3.5

Carbon 1.7 Residue 54.8

Water 130.3 Solvent loss 13.3


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24. 2-[[4-(2-Methoxyethyl)phenoxy]methyl-oxirane


Water take in Reactor add Epichlorohydrine and charge in 4.Methoxy Ethyl Phynol. After

completing reaction we will get the product.

Route of Synthesis:

Mass Balance:

STAGE-1 (Epoxide)


4MEP 100.00 Epoxide 126.00

Epichlorohydrine 100.00 Effluent 354.00

Caustic soda 30.00

Water 250.00


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25. 3''-acetyl-2''-hydroxy-4-(4 phenylbutoxy) benzanilide


Stage-1:

To a stirred solution of Dimethyl Formamide and Methylene dichloride is added 4-(4-

phenylbutoxy)benzoic acid. Charge drop wise thionyl chloride. After completion, distil out

Methylene Dichloride under vacuum. Cha

rge this reaction mass to stirred solution of 3-amino 2-hydroxy acetophenone in Methylene

dichloride and pyridine at 0-5°C. After completion of reaction, charge Hydrochloric acid and

separate layers. Wash with Sodium bicarbonate solution and evaporate organic layer to

yield N-(2-hydroxy-3- (3-oxo-3-(1H-tetrazol-5-yl) propanoyl)phenyl)- 4 - (4-phenylbutoxy)

benzamide.

Route of Synthesis:

Mass Balance:

Stage-1

Input QTY. (kgs) Output QTY. (kgs)

4-(4-phenylbutoxy)benzoic acid 100.00 Stage -1 125.00


Ethanone

57.60 Methylene Dichloride(Reco) 570.00

Methylene Dichloride(F/R) 588.00 Solvent Loss 18.00

Dimethyl Formamide 5.00 Effluent 519.30

Thionyl Chloride 59.00 Organic Residue 27.10

Pyridine 89.60 Process Emissions(SO2) 19.80


Sodium Bicarbonate 30.00

Water 150.00

Total 1279.20 Total 1279.20

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Group – II

26. Prasugrel Hydrochloride


Stage-I:

Charge 2-Bromo-1-cyclopropyl-2-(2-flourophenyl)ethanone, 5,6,7,7a-tetrahydrothieno[3,2-

c]pyridine-2-(4H)-one, potassium hydroxide and MeOH. Heat the reaction mass to reflux for

4 hrs. Cool the reaction mass to RT. Filter the reaction mixture distil off solvent from the

filtrate and water to residue and cool it to 0-5°C. Filter the solid formed spin dry and unload

the material dry the material at 50-60°C for 2 hrs. Cool the drier and unload the material.

Stage-II:

Charge stage-I material,Methyl Ethyl Ketone, and acetic anhydride, heat the reaction mass

to reflux for 4 hrs. Cool the reaction mass to 5-10°C and filter spin, dry and unload the

material. Dry the material at 50-60°C for 2hrs. Cool the drier and unload the material

(Prasugrel).

Stage-III:

Charge Stage-II material, methanol andHCl and heat the reaction mass to reflux for 4 hrs.

Cool the reaction mass and filter, spin, dry and unload the material. Dry the material at 50-

60°C for 2 hrs. Cool the drier and unload the material (prasugrel crude).

Stage-IV:

Charge Stage-III material, Acetone and Methanol. Heat the reaction mass to reflux for 2 hrs.

Cool the reaction mass to 0-5°Cand filter, spin, dry and unload the material. Dry the material

at 50-60°C for 2 hrs cool the drier and unload the material.

of 177

Route of Synthesis:

of 177

Material Balance:

Stage-I


Stage-I 49 2-Bromo-1-cyclopropyl-2-(2-


44

Recovery Methanol 123

Loss of Methanol 9 5,6,7,7a-tetrahydrothieno[3,2-


27

Effluent 364.86

Potassium Hydroxide 11 Residue 8.14

Methanol 132

Purified water 340

Total 554 Total 554

Stage-II


Stage-I 49 Stage-II 50

Acetic anhydride 16 Recovery Methyl ethyl ketone 137

Methyl ethyl ketone 147 Loss of Methyl ethyl ketone 10

Residue 15

Total 212 Total 212

of 177

Stage-III


Stage-II 50 Stage-III 52

Hydrogen Chloride 5 Recovery Methanol 142

Methanol 150 Loss of Methanol 8

Residue 3

Total 205 Total 205

Stage-IV


Stage-III 52 Prasugrel Hydrochloride 50

Acetone 156 Recovery Acetone 147.5

Methanol 156 Recovery Methanol 148

Loss of Acetone 8.5

Loss of Methanol 8

Residue 2

Total 364 Total 364

of 177

27. 5-[2-Cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl] -5,6,7,7a-

tetrahydrothieno[3,2-c]pyridin-2(4H)-one


Stage-I:

Charge 2-Bromo-1-cyclopropyl-2-(2-flourophenyl)ethanone, 5,6,7,7a-tetrahydrothieno[3,2-

c]pyridine-2-(4H)-one, potassium hydroxide and MeOH. Heat the reaction mass to reflux for

4 hrs. Cool the reaction mass to RT. Filter the reaction mixture distil off solvent from the

filtrate and water to residue and cool it to 0-5°C. Filter the solid formed spin dry and unload

the material dry the material at 50-60°C for 2 hrs. Cool the drier and unload the material.

Route of Synthesis:

Material Balance:

Stage-I


Stage-I 49 2-Bromo-1-cyclopropyl-2-(2-


44

Recovery Methanol 123

Loss of Methanol 9 5,6,7,7a-tetrahydrothieno[3,2-


27

Effluent 364.86

Potassium Hydroxide 11 Residue 8.14

Methanol 132

Purified water 340

Total 554 Total 554

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28. Dabigatran


Stage-I:

The propanoic acid methyl ester derivate of formulae-I is dissolved in ethanol and acetic

acid hydrogenated with damp Pd/C at RT at 2 bar hydrogen pressure. After completion of

the reaction the catalyst is filtered off and dissolved in ethanol was added to filtrate. To get

formulae-II precipitated out which was filtered off and dried.

Stage-II:

The Tosylate salt obtained in the stage-I was dissolved in acetone and the mixture is

combined with hexyl chloroformate in presence of potassium hydroxide at temperature

15°C. After completion of the reaction the precipitated product is filtered off and washed

with acetone mixture. The resulting crude is crystallized with water.

Route of Synthesis:

Material Balance

Stage-I


Stage-I 42.3

Recovery Ethanol 1225

Loss of Methanol 25

Carbon dioxide 3.7

3-[(1-Methyl-2-{[4-(5-oxo-4,5-dihydro-

[1,2,4]oxadiazol-3-yl)-phenylamino]-

methyl)-1H benzoimidazole-

5carbonyl)-pyridin-2-ylamino]-

propionic acid ethyl ester

48.5

Residue 25

P-toluene sulphonic acid 12.5

Acetic acid 10

Ethanol 1250

Total 1321 Total 1321

of 177

Stage-II


Stage-I 42.3 Dabigetran 50

Hexachlorofomate 14 Recovery Acetone 574.8

Acetone 600 Loss of Acetone 25.2

Potassium Hydroxide 4.8 Potassium chloride 6.3

Hydrochloric acid 0.19 Effluent 501.6

Purified water 500 Residue 3.3


of 177

29. Famotidine


Stage-1:

1, 3-Dichloro acetone reacts with Guanylthiourea in the presence of Acetone as solvent

media to give Stage-2 as product.

Stage-2:

Stage-1 product reacts with Thiourea, N-Sulfamyl-3-chloropropionamidine, Sodium

hydroxide and acetic acid in the presence of Methanol as solvent media to give Stage-2 as

product.

Stage-3

Stage-2 product reacts with ammonia in the presence of Methanol as solvent media to give

Famotidine as product.

Chemical Reaction:

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Material Balance:

Stage-1


1,3-Dichloro acetone 53.00 Stage-1 88.97

Guanylthiourea 50.00 Acetone Rec. 161.00

Potassium Iodide 2.40 Generated water 7.51

Acetone 170.00 Inorganic solid waste 2.40

Organic solid waste 7.52

Solvent Loss 8.0


Stage-2


Stage-1 88.97 Stage-2 125.70

Thiourea 25.13 Methanol Rec. 3228.00

Sodium Hydroxide 40 Generated water 12.00

N-Sulfamyl-3-

chloropropionamidineHCl

74.00 Inorganic solid waste 70.60

Acetic acid 20.00 Organic solid waste 39.80

Methanol 3397.00 Solvent loss 169.00

Total 3645.10 Total 3645.10

Stage-3


Stage-2 125.70 Famotidine 100.00

Ammonia (23%) 24.00 Methanol Rec. 36.00

Acetic acid 5.00 Effluent Water 574.00

Activated Carbon 6.00 Spent Carbon 6.00

Water 525.00 Organic Residue 7.70

Solvent loss 1.00


of 177

30. N-[(2'-Cyano[1,1'-biphenyl]-4-yl)methyl]-L valine methyl ester


Stage-1:

L-Valine reacts with Methanol in presence of Methanol as solvent media to give Stage-1 as

product.

Stage-2:

Stage-1 product reacts with 4-Bromomethyl-biphenyl-2-carbonitrile in presence of

Methanol as solvent media to give Stage-2 as product.

Route of Synthesis:

of 177

Mass Balance:

Stage-I

Input QTY.(kgs) Output QTY.(kgs) L-Valine 45.00 Stage-1 50.00 Thionyl Chloride 45.70 Methanol Rec. 758.00 Methanol 800.00 Toluene Rec. 474.00 Toluene 500.00 Organic Residue 8.33

Solvent Loss 65.00

Process Loss 35.37 Total 1390.70 Total 1390.70

Stage-II

Input QTY.(kgs) Output QTY.(kgs) Stage-1 50.00 Stage-2 90.00 4-Bromomethyl-biphenyl-2-carbonitrile 82.00 Toluene Rec. 565.00 Potassium carbonate 45.00 Effluent Water 569.78 Toluene 600.00 Organic Residue 9.22 Water 500.00 Process Loss 13.00

Solvent Loss 30.00 Total 1277.00 Total 1277.00

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31. Amlodipinbesylate


Stage I:

Charge toluene, phthalic anhydride and mono-ethanol amine into the reactor. Heat the

mass to reflux. Maintain for 4 hours at reflux. After completion of the reaction, cool the

mass below 35°C and charge water. Stir the mass and settle for 1 hour. Discard bottom

aqueous layer to ETP. Cool the mass to 10-15°C. Centrifuge the material and wash with

toluene.

STAGE –1A: Charge Methyl acetoacetate and ammonia solution into the reactor and maintain for 6 hours. Filter the mass.

STAGE –II:

Charge toluene, sodium hydride and Stage I compound into the reactor. Cool the mass to 0-

5°C. Add ethyl 4-chloro acetoacetate into the reactor maintaining the temperature of the

reaction mass at 0-5°C. After completion of the reaction, charge diluted hydrochloric acid

and sodium chloride. Filter the mass and distil off toluene about 50% of volume and cool the

mass slowly to 10-15°C. Centrifuge the mass and wash with toluene.

STAGE –III:

Charge hexane and pyridine in the reactor, heat the reaction mass to 50°C. Add

orthochlorobenzaldehyde into the reactor for 4 to 5 hours at 50-55°C. Maintain the mass for

4 hours and distil off hexane completely below 55°C. Cool the mass and charge toluene into

the reactor followed by acetic acid. Charge stage-II compound into the reactor and maintain

for 4 hours at room temperature. After completion of the reaction, Charge water into the

reactor and stir. Discard the bottom aqueous layer to ETP. Distil off toluene completely

under vacuum below 85°C. Cool the mass and charge ethyl acetate. Stir and cool the mass to 0-5°C. Centrifuge the material and wash with ethyl acetate.

Stage – IV:

Charge hexane, Stage III compound and Stage-1A compound into the reactor. Heat the

reaction mass to reflux and maintain for 4 hours. Cool the mass to 25-30°C. Centrifuge the

material and wash with hexane.

Stage V:

Charge monomethyl amine and Stage IV material into a reactor and heat to 75-80°C. After

completion of the reaction, cool the mass to room temperature. Centrifuge the material to

produce Amlodipine Base compound.

STAGE –VI:

Charge methanol, Amlodipine Base compound into a reactor and add Benzene sulphonic

acid slowly for 3-4 hours at 45-50°C. After completion of reaction, distil off methanol

completely. Charge ethyl acetate into the reactor and cool to 0-5°C. Centrifuge the material

and wash with water followed by ethyl acetate. Dry the material at 50-55°C to give

Amlodipinbesylate.

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Route of Synthesis:

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Material Balance:

Stage-I

INPUT QTY.(KGS) OUTPUT QTY.(KGS) Phthalic anhydride 100 Stage-I 100 Monoethanol amine 45 Solv Rec (Toluene) 190 Toluene 196 Residue 25 Purified Water 200 Solvent loss 6 Effluent 220 Total 541 Total 541

Stage-1A


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Stage-II

INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage I 100 Stage-II 125 Ethyl Chloroaceto acetate 55 Solv Rec (Toluene) 210 Hcl 5 Residue 131 Acetic acid 18 Solvent loss 5

Sodium chloride 50

Sodium hydride 28

Toluene 215 Total 471 Total 471

Stage-III

INPUT QTY.(KGS) OUTPUT QTY.(KGS) Ortho Chlorobenzaldehyde 40 Stage III 150 Hexane 191 Sol. Rec (Tol) 488 Piperidine 2 Sol Rec.(EA) 343 Acetic acid 25 Sol Rec. (Hex) 183 Toluene 500 Aq. Effiuent 147 Purified Water 130 Residue 25 Stage II 125 Solvent loss 27 Ethyl acetate 350 Total 1413 Total 1413

Stage-IV

INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-III 150 Stage IV 150 Stage-IA 35 Sol Rec (Hex) 342 Hexane 356 Residue 35

Solvent loss 14 Total 541 Total 541

Stage-V

INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage IV 150 Stage V 100 MMA 175 Aq. Effluent 225 Total 325 Total 325

Stage-VI

INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage V 100 Stage VI 100 Benzene Sulfonic acid 64 Sol. Rec(MeOH) 195 Methanol 200 Sol. Rec (EA) 243 Ethyl acetate 250 Aq. Effiuent 144 Purified water 100 Residue 20


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32. Amlodipine base


Stage I:





toluene.

STAGE –1A:



STAGE –II:






STAGE –III:







under vacuum below 85°C.

Cool the mass and charge ethyl acetate. Stir and cool the mass to 0-5°C. Centrifuge the

material and wash with ethyl acetate.

Stage – IV:




Stage V:

Charge monomethyl amine and Stage IV material into a reactor and heat to 75-80°C. After

completion of the reaction, cool the mass to room temperature. Centrifuge the material to

produce Amlodipine Base compound.

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Route of synthesis:

of 177

Material Balance:

Stage-I


Stage-1A


Stage-II


Sodium chloride 50

Sodium hydride 28


of 177

Stage-III

INPUT QTY.(KGS) OUTPUT QTY.(KGS) Ortho Chlorobenzaldehyde 40 Stage III 150 Hexane 191 Sol. Rec (Tol) 488 Piperidine 2 Sol Rec.(EA) 343 Acetic acid 25 Sol Rec. (Hex) 183 Toluene 500 Aq. Effluent 167 Purified Water 150 Residue 25 Stage II 125 Solvent loss 27 Ethyl acetate 350 Total 1383 Total 1383

Stage-IV



Stage-V

INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage IV 150 Stage V 100 MMA 275 Aq. Effluent 325 Total 425 Total 425

of 177

33. 2,4-dihydro-4-[(4-(4-hydroxyphenyl)-1-piperazinyl)phenyl]-2-(1-

methylpropyl)-3h-1,2,4-triazole-3-one









Stage-II:

Charge DMF, palladium carbon and 1-(4-Methoxyphenyl)-1-(4-nitrophenyl) piperazine into

the reactor. Heat the mass to 50-55°C. Pass hydrogen gas for 18 hours. After completion of

the reaction, cool the mass below 35°C and filter the mass. Cool the filtrate to 0-5°C and

maintain. Centrifuge the mass to produce 1-(4-Methoxyphenyl)-1-(4-aminophenyl)

piperazine.

Stage-III + IV:

Charge Methylene chloride and 1-(4-Methoxyphenyl)-1-(4-aminophenyl) piperazine

compound into a reactor. Heat the mass to 35-45°C. Add phenyl chloroformate for 5-6 hours

at same temperature. After completion of the reaction, charge water into the reactor.

Separate the layers. Discard aqueous layer and charge organic layer. Distill off Methylene

chloride completely and charge n-butanol into the reactor. Heat the mass to 55-60°C. Add

hydrazine hydrate into the reactor. Maintain for 4 hours at same temperature and cool the

mass. Centrifuge the mass and wash with n-butanol to produce 2,4-Dihydro-4-[(4-

methoxyphenyl)-1-piperazinyl]phenyl hydrazine carboxamide.

Stage-V:

Charge DMF and carboxamide compound into the reactor and heat to 70-75°C. Add

formanidineacetate into the reactor slowly. After completion of the reaction, cool the mass

and centrifuge, to produce 2,4-Dihydro-4-[4-[(4-methoxyphenyl)-1-piperazinyl phenyl]-3H-

1,2,4-triazole-3-one.

Stage-VI:

Charge 2-bromobutane, potassium carbonate and triazole compound into a reactor. Heat to

reflux and maintain for 8 hours. After completion of reaction filter the mass and distil off 2-

bromebutane completely. Charge DMF into the reactor and acidify the mass with

hydrochloric acid. Centrifuge the material and wash with DMF to produce 2,4-Dihydro-4-[4-

[(4- methoxyphenyl)-1-piperazinyl phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazole-3-one.

Stage-VII:

Charge hydrobromic acid and stage-VI compound into a reactor and heat the mass to reflux.

After completion of the reaction, distil off HBr completely and charge water into the reactor.

Neutralize the mass with soda ash. Centrifuge the mass and wash with water to produce

2,4- Dihydro-4-[4-[(4-hydroxyphenyl)-1-piperazinyl] phenyl]-2-(1-methylpropyl)-3H-1,2,4-

triazole-3-one (ITR-INT-B).

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Route of Synthesis:

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Mass Balance:

Stage-01 Int-B











of 177

Stage-02 Int-B


Stage-I 132.4 Stage-II 118.3


Palladium carbon 0.1 Gas loss 5.0

Hydrogen gas 10 Residue 19.2

Solvent loss 7.0


Stage-03-04 Int-B


Stage-II 118.3 Stage-IV 136.0

Phenyl chloroformate 78.6 Solvent Rec (MDC) 240.0

Sodium bicarbonate 71.0 Solvent Rec (Butanol) 145.2

Methylene chloride 246.0 Aq. Effluent 220.8

Hydragin hydrate 65.0 Residue 41.8

n-Butanol 147.8



Stage-05 Int-B


Stage-IV 136.0 Stage-V 121.2

Formamidine acetate 63.6 Solvent Rec (DMF) 380.3

Dimethyl formamide 390.0 Residue 78.3

Solvent loss 9.7


Stage-06 Int-B


Stage-V 121.2 Stage-VI 92.9

2-Bromo butane 125.2 Solvent Rec (DMF) 349.7

Potassium carbonate 51.0 Solvent Rec (2-BB) 92.0



Solvent loss 9.4


Stage-07 Int-B


Stage-VI 92.9 ITR-INT-B 78.0

Hydrobromic acid 961.9 Hydrobromic acid rec 935.5

Soda ash 86.7 Aq. Effluent 217.6



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34. Metoprolol Tartrate


Water take in Reactor add Epichlorohydrine and charge in 4.Methoxy Ethyl Phynol Maintain

and add Caustic soda solution reaction in 7 hours and water wash and distill it. Product

unload in HDPE Carboys.

Metoprolol Base take into Ethyl acetate and Methanol and a solution of Tartric acid in

Methanol at 60-65oC in 4 hours reflux and cooling. Product centrifuge and wash with Ethyl

Acetate. Finished product dry in FBD and packed in HDPE container.

Route of Synthesis:

Mass Balance:

Stage-I (Epoxide)


4MEP 100.00 Epoxide 126.00


Caustic soda 30.00

Water 300.00


STAGE-2 (Metoprolol Base)


Stage-1 126.00 Metoprolol Base 149.00

MIPA 300.00 Effluent 767.00

Water 400.00 Toluene Reco 260.00


HCL 60.00

Caustic lye 30.00

Total 1316.00 Total 1316.00

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STAGE-3 (Metoprolol Tartrate)


Stage-2 100.00 Metoprolol Tartrate 118.00

Ehtyl Acetate 600.00 Ethyl acetate reco 540.00

Tartric Acid 25.00 Methanol reco 315.00


Dry loss 7.00

Total 1075.00 Total 1075.00

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35. 1-(Isopropylamino)-3-[4-(2-methoxyethyl) phenoxy]-2-propanol




unload in HDPE Carboy’s.

Route of Synthesis:

Mass Balance:

STAGE-1 (Epoxide)


4MEP 100.00 Epoxide 126.00


Caustic soda 30.00

Water 300.00








HCL 60.00

Caustic lye 30.00

Total 1267.00 Total 1267.00

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36. Metoprolol Succinate




unload in HDPE Carboy’s.

Metoprolol Base take into Ethyl acetate and Methanol and a solution of Succinic acid in

Methanol at 60-65oC in 4 hours reflux and cooling. Product centrifuge and wash with

Ethyl Acetate. Finished product dry in FBD and packed in HDPE container.

Route of Synthesis:

Mass Balance:

STAGE-1 (Epoxide)


4MEP 100.00 Epoxide 126.00


Caustic soda 30.00

Water 250.00








HCL 60.00

Caustic lye 30.00

Total 1216.00 Total 1216.00

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STAGE-3 (Metoprolol Succinate)


Stage-2 100.00 Metoprolol Succinate 112.00

Ehtyl Acetate 400.00 Effluent 75.00

Succinic Acid 21.00 EA Reco 360.00


Dry loss 4.00


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37. Ketoconazole Process Description: Stage I:

CBB is reacted with IMD in the presence of DMF as solvent. The reaction mass is quenched in sodium bicarbonate solution and the product is extracted with toluene. The aqueous layer is kept for IMD recovery. The organic layer containing the product is reacted with sodium hydroxide solution. After completion of reaction, the pH of the mass is adjusted with hydrochloric acid. mass is diluted with water and centrifuged. The wet cake is dissolved in ethyl acetate and treated with carbon. The mass is filtered and the ethyl acetate is distilled off. The residue is cooled and centrifuged. The mass is dried to produce KT-I.

Stage II:

KT-I is reacted with PTSC in the presence of sodium carbonate and methylene chloride as

solvent. The reaction mass is diluted and the organic layer separated. Methylene chloride is

distilled off completely from the organic layer and the residue is diluted with methanol and

water. The mass is centrifuges and washed with methanol and water mixture. The mass is

dried to produce Cis-Tosylate (KT-II).

Stage-III:

Cis-Tosylate (KT-II) is reacted with Para hydroxyl phenyl N-acetyl piperazine and sodium

methoxide in the presence of dimethyl sulfoxide as solvent. After completion of the

reaction, sodium hydroxide solution is charged into the reactor and maintained. The mass is

centrifuged. The wet cake is treated with water and further by acetone. The wet cake is

taken for next stage.

Stage IV:

The wet cake is dissolved in ethyl acetate and methanol, and treated with carbon. The mass

is filtered and the solution distilled off. The residue is cooled and centrifuged. The material is

dried to produce Ketoconazole.

Route of Synthesis:

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Material Balance:

Stage-I


CBB 780 Stage-1 450

IMD 693.3 IMD Rec 360

DMF 37.2 Toluene Rec 2207.0

Toluene 2275.5 Ethyle Acetate 1620.0

Sodium Bicarbonate 148.2 Aq. Effluent 1599.4

Sodium hydroxide 120.0 Spent carbon 12.0

Water 705.0 Residue 130.0

HCl 156 Process loss 254.9

Ethyl Acetate 1706.4

Activated Carbon 6.0

Vacuum Salt 6.0


of 177

Stage-II


Stage-1 450.0 Stage-2 600.0

Methylenechloride 3217.5 Methylenechloride Rec 3024.0

P-Toluene Sulfonyl Chloride 465.0 Methanol Rec 1375.0

Sodium Carbonate 307.5 Aq. Effluent 778.0

HCl 12.0 Process Loss 400

Methanol 1425.0

Water 420


Stage-III


Stage-2 600 Stage-3 650.0

PeraHydroxy phenyl n-acetyl piperazine 285.0 Dimethyl Solfoxide Rec 779.0

Dimethyl Solfoxide 847.0 Acetone Rec 300.0

Sodium methoxide powder 70.0 Aq. Effluent 408.0

Sodium Hydroxide 50.0 Residue 59.0

Acetone 240.0 Process loss 68.0

Methnol 7.0

Water 165.0


Stage-IV


Stage-3 650 Ketoconazole 510.0

Ethyl Acetate 2220.0 EA + Methanol Rec 2550.0

Methanol 464.0 Spent Carbon 40

Activated Carbon 20 Residue 80.0

Proess Loss 174.0


of 177

38. Phthaloyl amlodipine


Stage I:





toluene.

STAGE –1A:



STAGE –II:






STAGE –III:







under vacuum below 85°C.

Cool the mass and charge ethyl acetate. Stir and cool the mass to 0-5°C. Centrifuge the

material and wash with ethyl acetate.

Stage – IV:




Route of Synthesis:

of 177

of 177

Material Balance:

Stage-I


Stage-1A


Stage-II


Sodium chloride 50

Sodium hydride 28


Stage-III

INPUT QTY.(KGS) OUTPUT QTY.(KGS) Ortho Chlorobenzaldehyde 40 Stage III 150 Hexane 191 Sol. Rec (Tol) 488 Piperidine 2 Sol Rec.(EA) 343 Acetic acid 25 Sol Rec. (Hex) 183 Toluene 500 Aq. Effiuent 267 Purified Water 250 Residue 25 Stage II 125 Solvent loss 27 Ethyl acetate 350 Total 1483 Total 1483

Stage-IV



of 177

39. 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl] phenyl]-2-(1-

methylpropyl)-3H-1,2,4-triazol-3-one









Stage-II:





piperazine

Stage-III + IV:









Stage-V:




1,2,4-triazole-3-one

Stage-VI:





[(4- methoxyphenyl)-1-piperazinyl phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazole-3-one.

of 177

Route of Synthesis:

of 177

Mass Balance:

Stage-01 Int-B











Stage-02 Int-B






Solvent loss 7.0


Stage-03-04 Int-B







n-Butanol 147.8



of 177

Stage-05 Int-B





Solvent loss 9.7


Stage-06 Int-B







Solvent loss 9.4


of 177

GROUP – III

40. Montelukast Sodium

Process Description: Stage-I: 1-(Hydoxy methyl) cyclo propane Acetonitrile (MEC-4) is reacted with methane sulfonyl

chloride in presence of Diisoprpylethyl amine, and the product is further treated with Thiol

acetic acid to give MAN.

Stage-II: Condensation of MAN and (2-(2-(3(S)-(3-(2-(7-Chloro-2-quinolinyl) ethenyl) phenyl-3-

(methane sulfonyloxy) propyl)-2-propanol) (QUID-8) in the presence with n-butyl lithium in

the presence of toluene and Dimethyl foramide which on further hydrolysis with Caustic lye

to give MOK-1 –Nitrile

Stage-III: MOK-1 Nitrile underwent sodium hydroxide hydrolysis in the presence of toluene to give MOK-1. Stage-IV: MOK-1 treated with t-butyl amine protection with acetone acid to give MOK-2 butyl amine.

Stage- V: MOK-2 t-butylamine on further treatment with caustic flakes to give sodium Montelukast

(MOK-3). On further carbon purification with methanol to give Pure MK-3 salt (Montelukast

Sodium).

Route of Synthesis:

of 177

Mass Balance:

Stage-I Input Qty.(KGS) Output Qty.(kgs)

N-vinyl pyrrolidone 108.1 Stage-I 96.5 Thiol acetic acid 74 Acetic acid 45.6 Diisopropyl ethylamine 6 Toluene recovered 1447.5 Toluene 1500 Toluene loss 7.5 Water 1000 Toluene residue 45 Methane sulfonyl Chloride 15 N-vinyl pyrrolidone 23.7

Thiol acetic acid 16.3

Diisopropyl ethylamine 6

Methane sulfonyl chloride 15

Water 1000 Total 2703.1 Total 2703.1

Stage-II Input QTY.(kgs) Output QTY.(kgs)


Thiophene-2-ethylamine 347.4 Water generated during reaction 11.1

Toluene 2000 Toluene recovered 1940 Water 600 Toluene loss 10 Acetic acid 10 Toluene residue 50 Sodium chloride 50 Stage-I 17.9 Carbon 5 Thiophene-2-ethylamine 64.3

Acetic acid 10

Carbon 5

Sodium chloride 50

Water 600 Total 3108.9 Total 3108.9

of 177

Stage-III


Stage-II 350.6

Stage-III (Crude Nateglinide Form

H) 235.6

Sodium hydroxide 24.7 Sodium methoxide 21.7 Methanol 1219.8 Ammonia 6.8 Toluene 1700 Methanol recovered 1152

Water 800 Methanol loss 6

Acetic acid 30 Methanol wastewater 12

Sodium chloride 70 Methanol residue 30

HCl for NaOH neutralization 7.9 Toluene recovered 1632

Toluene loss 6.8

Toluene residue 61.2

Stage-II 122.7

Methanol 6.9

Acetic acid 30

Sodium hydroxide 8.7

Sodium chloride 70

Water 784

NaCl from NaOH neutralization 12.7

Water from NaOH neutralization 3.9


Stage-IV


Stage-III 235.6 Stage-IV 198.7

Tertiary butyl amine 29.4 Acetone recovered 1536

Acetone 1600 Acetone loss 7.2

Toluene 2000 Acetone residue 56.8

Carbon 5 Toluene recovered 1920

Toluene loss 10

Toluene residue 70

Stage-III 58.9

Tertiary butyl amine 7.4

Carbon 5 Total 3870 Total 3870

of 177

Stage-V

Input QTY.(kgs) Output QTY.(kgs) Stage-IV 198.7 Montelukast Sodium 150 Sodium hydroxide 62.1 Tert-butylamine 18 Mdc 1800 Water generated during reaction 4.4 Acetic acid 25 MDC recovered 1737 Water 1000 MDC loss 9 Methanol 1000 MDC residue 54 Carbon 5 Methanol recovered 970 HCl for NaOH neutralization 47.6 Methanol loss 4

Methanol residue 26

Stage- IV 36.1

Acetic acid 25

Carbon 5

Sodium hydroxide 52.2

Water 947.9

NaCl from NaOH neutralization 76.3

Water from NaOH neutralization 23.5


of 177

41. Valsartan


Stage-1:

L-Valine reacts with Methanol in presence of Methanol as solvent media to give Stage-1 as

product.

Stage-2:

Stage-1 product reacts with 4-Bromomethyl-biphenyl-2-carbonitrile in presence of

Methanol as solvent media to give Stage-2 as product.

Stage-3: Stage-2 product reacts with Valeryl chloride in presence of Methanol as solvent media to give Stage-3 as product.

Stage-4:

Stage-3 product reacts with Sodium azide; Tri butyl tin chloride undergoes

Hydrogenation in presence of Methanol as solvent media give Valsartan as product.

Route of Synthesis:

of 177

of 177

Mass Balance:

Stage-I

Input QTY.(kgs) Output QTY.(kgs) L-Valine 45.00 Stage-1 50.00 Thionyl Chloride 45.70 Methanol Rec. 758.00 Methanol 800.00 Toluene Rec. 474.00 Toluene 500.00 Organic Residue 8.33

Solvent Loss 65.00


Stage-II

Input QTY.(kgs) Output QTY.(kgs) Stage-1 50.00 Stage-2 90.00 4-Bromomethyl-biphenyl-2-carbonitrile 82.00 Toluene Rec. 565.00 Potassium carbonate 45.00 Effluent Water 569.78 Toluene 600.00 Organic Residue 9.22 Water 500.00 Process Loss 13.00


Stage-III

Input QTY.(kgs) Output QTY.(kgs) Stage-2 90.00 Stage-3 100.00 Valeryl Chloride 34.00 Toluene Rec. 660.00

Toluene 700.00 Effluent Water 444.80 TEA 20.00 Inorganic Solid Waste 10.00 Water 500.00 Organic Residue 16.93

Process Loss 12.27


Stage-IV

Input QTY.(kgs) Output QTY.(KGS) Stage-3 100.00 Valsartan 100.00 Sodium Azide 16.00 Toluene Rec. 660.00 Tri Butyl tin Chloride 80.00 MDC Rec. 475.00 Hydrogen Gas 0.50 Xylene Rec. 228.00 Sodium Hydroxide 20.00 N-Hexane Rec. 190.00 Xylene 240.00 Effluent Water 577.30 Toluene 700.00 Spent Carbon 10.00 Water 500.00 Organic Residue 9.22


of 177

42. Venlafaxine Hydrochloride


Anisole reacts with Aluminium chloride and acetyl chloride in methylene chloride togive 4-

methoxy acetophene and 4-methoxy acetophenone reacts with dimethylformamide,

sodium acetate and sulfur to give thioacetamide reacts with Cyclohexanone in presence of

grignard reagent togive N,N Dimethyl-2-(1-hydroxy cycloridehexahydrate, in methanol to

give N,N Dimethyl-2-(4-methoxyphenyl)ethyl amine which reacts with Borohydride and

nickel chloride hexahydrate, in methanol to give N,N Dimethyl-2-

(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyineor(+/-) 1-(2- Dimethylamino)-1-(4-

methoxyphenyl)ethyl) cyclohexanol, which further crystallized in hydrochloride formation

inisopropanol HCL and ethyl acetate as solvent to give final product Venlafaxine

hydrochloride.

Route of Synthesis:

of 177

Mass Balance:

Stage-I


4-Methoxy Benzoyl Cyanide 96.56 Stage-1 136.00

Methanol 349.52 Aqu Effluent 752.48

Sodium Methoxide 91.12 CFML 1957.04

Cyclohexanone 89.76 Toluene Reco 432.97

Toluene 481.08 Solvent Loss 48.11

Water 2228.08 Dry Loss 9.52

Total 3336.12 Total 3336.12

of 177

Stage-II

Input QTY.(kgs) Output QTY.(kgs) Acetic Acid 815.00 Venafaxine Hydrochloride 100.00 Stage-1 136.00 Catalyst 5.00 Catalyst 5.00 Acetic Acid reco 773.00 Caustic soda 477.00 Reco loss 42.00 Formic soda 194.00 Aqu effluent 1457.00 Formaldehyde 112.00 Sodium sulphate 27.00 Hydrochloric acid 251.00 Hyflo 4.00

Ethyl acetate 2253.00 Carbon 1.00 Sodium Sulphate 27.00 Ethyl Acetate Reco 2139.00 Sodium chloride 34.00 Reco loss 114.00 Hyflo 4.00 IPML 1550.00 IPA 1460.00 Dry Loss 18.00

IPA HCL 109.00

Activated Charcoal 1.00

Water 352.00

Total 6230.00 Total 6230.00

of 177

43. Levocetirizine Dihydrochloride


Stage-I:

1-[(4-Chlorophenyl) phenyl methyl]-4-[(phenyl sulphonyl] piperazine is deprotectedwith 4-

Hydroxy benzoic acid in Hydro bromic acid then is condensed with 2(2-

Chloroethoxyacetamide) in presence of Sodium carbonate in toluene and is reacted with

sodium hydroxide and Hydrochloric Acid in acetone to give Levocetrizine Di hydrochloride as

product.

Route of Synthesis:

of 177

Mass Balance:

Stage-I


LevocetirizineDihydrochloride 50 1-[((4 Chlorophenyl)phenyl)methyl] -

4-[(phenylsulphonyl)]piperazine

46.20

Recovery Toluene 1440

2(2-Chloroethoxy )acetamide 14.90 Recovery MDC 1767

4-Hydroxy benzoic acid 16 Recovery Acetone 442

Hydrobromic acid 8.80 Loss of Toluene 75

Sodium hydroxide 8.70 Loss of MDC 93

Hydrochloric acid 15.80 Loss of Toluene 23

Sodium carbonate 11.50 Activated Carbon 4

Potassium iodide 1.70 Effluent 1000.24

Toluene 1515 Residue 41.36

MDC 1860

Acetone 465

Activated carbon 4

Purified water 968

Total 4935.60 Total 4935.60

of 177

44. Pregabalin


Sodium Hydroxide solution in Process water is chilled at 0-10°C and then charge

R-(-)-3- (Carbamoylmethyl)-5-methylhexanoic acid [R-(-)-CMH]. Addition of liquid Bromine is

done at 0- 5°C then raise the temperature of the reaction mass up to 30-35°C. After reaction

monitoring, raise the temperature of the reaction mass to 55-60°C and apply carbon

treatment. The clear filtrate is then received in another reactor. Excess water is distilled off

from the reaction mass. The reaction mixture is acidified with concentrated Hydrochloric

acid. Reaction mass is then up to 80-85°C and after that gradual cooling to 25-30°C. The

material is centrifuged after maintaining of the reaction mass at 25-30°C for 4-6 hrs. The

dry material is then charged in IPA and raises the temperature to 80-85°C. Add DM water to

reaction mass at 80-85°C. Filter the clear reaction mass and chill it to 8-12°C. The material is

then centrifuged and dried in under vacuum.

Route of Synthesis:

Mass Balance:

Stage-1


Sodium Hydroxide 347.2 Stage-1 162.5

4-CMH 250.00 Spent carbon and hyflo 28.00

Liquid Bromine 224.00 Spent ML 2623.7

Hyflo 12.50 Loss on drying 62.5

Activated carbon 3.00


Process water 1590.00

Total 2877.00 Total 2877.00

Stage-2


Stage-1 215.00 Pregabalin 182.8

IPA 1290.00 Spent ML 1750.00

DM water 460.00 Loss on drying 32.2

Total 1965.00 Total 1965.00

of 177

45. Veratric Acid


Stage -I:

Catechol is methylated by Dimethyl sulphate in presence of aqueous alkaline solution and

gives Veratrol (Veratric acid Stage-I) as an organic layer.

Stage II:

Veratric acid Stage-I (Veratrol) is acylated with Acetyl chloride in presence of anhydrous

aluminum chloride in Methylene dichloride solvent. Reaction mass is quenched in chilled

Hydrochloric acid solution to get Veratric acid Stage-II.

Stage III:

Veratric acid Stage-II (Acetyl Veratrol) is oxidized with Sodium hypochlorite and further it is

hydrolysed by Hydrochloric acid to give Veratric acid. Isolate solid by centrifugation and dry

it.

Route of Synthesis:

of 177

Mass Balance:

Stage-I


Catechol 350 Stage-I 400

Dimethyl Sulphate 875 Effluent 1782

Sodium hydroxide 288 Salt 6

Purified water 695 Guicol 20


Stage-II



Methylene dichloride 1680 Recovery Methylene Dichloride 1440

Aluminium chloride 500 Loss of Methylene Dichloride 240

Acetyl chloride 395 Poly Aluminium chloride 3300

Hydrochloric Acid 240

Sodium Bicarbonate 10

Purified water 2200


Stage-III


Stage-II 445 Veratric Acid 380

Methylene dichloride 500 Recovery Methylene Dichloride 440

Sodium Hypo Chlorite 4675 Loss of Methylene Dichloride 60

Activated Carbon 10 Residue 15

Hydrochloric Acid 1120 Effluent 6875

Sodium meta bi sulphate 30 Activated Carbon 10

Purified Water 1000


of 177

46. Fluconazole


Stage-I:

Charge Methylene dichloride and aluminium chloride into the reactor. Cool the mass to

below 5°C. Charge 1,3-Difluorobenzene into the reactor. Add slowly chloroacetyl chloride

into the reactor for 4 to 5 hours below 10°C. Charge the reaction mass to ice and

hydrochloric acid. Stir the reaction mass for 4 hours and separate the layers. Distil off MDC

completely below 50°C. Charge isopropyl alcohol and 4-amino-1,2,4-triazole into the reactor

and maintain for 6 hours at 45-50°C. Cool the reaction mass to 10°C and centrifuge material

and dry to produce 2-(1H-1,2,4-triazole-1-yl)-2’,4’-difluoroacetophenone salt.

Stage-II:

Charge water, sodium nitrite and 2-(1H-1,2,4-triazole-1-yl)-2’,4’-difluoroacetophenone into

the reactor and heat to 50-60°C. Slowly add hydrochloric acid at 50-60°C and maintain for

12 hours. Cool the mass below 20°C and neutralize the reaction mass with ammonia

solution. Centrifuge the mass and wash with water. Dry the material to produce 1-(2,4-

difluorophenyl)- 2-(1H,1,2,4-Triazol-1-yl) ethanone.

Stage-III:

Charge Toluene, 1-(2,4-difluorophenyl)- 2-(1H,1,2,4-Triazol-1-yl) ethanone, potassium

hydroxide, 1,2,4,-Triazole and Trimethylsulphoxinium iodide into the reactor. Heat to reflux

and maintain for 12 hours.Distil off Toluene completely. Cool the reaction mass and charge

water into the reactor. Charge toluene into the reactor and stir for 30 minutes. Settle the

mass for 30 minutes. Separate the layers. Discard the bottom aqueous layer. Cool the mass

to 10°C and centrifuge. Dry the material to produce Fluconazole crude. Charge water, crude

and ammonia solution into the reactor. Check complete dissolution and charge carbon. Stir

for 30 min and filter over hyflow bed. Charge toluene and citric acid. Neutralize the mass

with hydrochloric acid. Stir for30 minutes and settle for 30 minutes. Separate the layers and

discard aqueous layer. Cool the mass. Centrifuge the mass and wash with toluene. Dry the

material to produce Fluconazole pharma.

Route of Synthesis:

of 177

Material Balance:

Stage-I


1,3-Difluorobenzene 200 Stage-I Compound 480 Aluminium Chloride 240 Sol Rec(MDC) 1050 Methylene Chloride 1200 Sol Rec (IPA) 740 Chloroacetyl chloride 210 AlCl3 gel for Rec. 1100 4-Amino-1,2,4-Triazole 162 Aq. Effluent 490 IPA 790 Residue 30 Sodium bicarbonate 15 Solvent loss 202


Ice & Water 1200 Total 4092 Total 4092

Stage-II


Stage-I Compound 480 Stage-II 370 Sodium Nitrite 118 Aq. Effluent 1778


Water 1100

Ammonia Solution 200 Total 2148 Total 2148

Stage-III


Stage-II 370 Stage-III 370 TrimethylSulphoxoniumIodiade 330 Sol Rec (Toluene) 550 1,2,4-Triazole 165 Aq. Effluent 1170 Potassium Hydroxide 235 Residue 50 Toluene 600 Solvent loss 60 Water 500 Total 2200 Total 2200

of 177

Stage-IV


Stage-III 370 Fluconazole 250 Toluene 1500 Solvent Reco (Tol) 1428 Activated carbon 15 Aq. Effuient 1478 Citric Acid 15 Spent Carbon 30 Ammonia solution 640 Spent hyflow 24 Hydrochloric Acid 180 Residue 50 Hyflowsupercell 12 Solvent loss 72 Water 600 Total 3332 Total 3332

of 177

47. Itraconazole


charge dimethyl formamide, cis-2[bromomethyl-2-(2,4 dichlorophenyl)1,3 dioxalane-4-

yl)methyl benzoate and 1H-1,2,4 triazole into a reactor. Charge sodium hydroxide solution

into the reactor.Heat to reflux and maintain for 8 hours. After completion of reaction, cool

the mass below 35°C and charge potassium carbonate. Stir the mass for 30 minutes and

filter. Charge the filtrate and distil off DMF completely. Charge water and toluene into the

reactor and stir for 30 minutes. Discard the bottom aqueous layer to ETP. Cool the organic

layer to 10-15°C. Centrifuge the material and wash with toluene. Dry the material at 60-65°C

to produce Cis-[2- (2,4-dichlorophenyl)-2-(1H,1,2,4-triazol-1yl methyl)1,3 dioxolan-

4yl]methanol.

Stage-II:

Charge methylene dichloride, Step-I compound and triethyl amine into a reactor. Slowly add

methane sulfonyl chloride into the reactor at 10-15°C. After completion of the reaction,

charge water and stir for 30 minutes. Separate the layers. Charge organic layer in to the

reactor and charge carbon. Stir for 30 minutes and filter the mass into another reactor. Add

hydrochloric acid into the reactor at 25-30°C. Cool the mass to 10-15°C. Centrifuge and wash

with methylene dichloride. Dry the material at 45-50°C to produce Cis-[2-(2, 4 -

dichlorophenyl) - 2 - (1H,1, 2, 4 - triazol - 1yl- methyl) 1,3-dioxolan-4yl]-methyl methane

sulfonate (ITR-INT-A). Process description–ITR-INT-B: Stage-I:








Stage-II:





piperazine.

Stage-III + IV:








of 177


Stage-V:




1,2,4-triazole-3-one

Stage-VI:





[(4- methoxyphenyl)-1-piperazinyl phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazole-3-one

Stage-VII:

Charge hydrobromic acid and stage-VI compound into a reactor and heat the mass to reflux.

After completion of the reaction, distil off HBr completely and charge water into the reactor.

Neutralize the mass with soda ash. Centrifuge the mass and wash with water to produce

2,4- Dihydro-4-[4-[(4-hydroxyphenyl)-1-piperazinyl] phenyl]-2-(1-methylpropyl)-3H-1,2,4-

triazole-3-one (ITR-INT-B)

ITRA-Stage-I/II/III:

Charge water, potassium hydroxide, Cis-(2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-yl-

methyl)-1,3-dioxalane-4-yl) methyl methane sulfonate and 2,4-Dihydro-4-[4-[(4-

hydroxyphenyl)-1-piperazinyl] phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazole-3-one into the

reactor. Heat the mass to 80-85°C and maintain for 6 hrs. Cool the mass below 35°C and

centrifuge. Charge the cake and DMF into a reactor and maintain for 1 hour at room

temperature. Centrifuge the mass and wash with DMF to produce Itraconazole crude. The

crude is treated with toluene, methanoland ethyl acetate and carbon to produce

Itraconazole pure.

Route of Synthesis:

of 177

of 177

Material Balance:

Stage-01 Int-A


Cis-Bromobenzoate 111.3 Triazole derivative 95.8

1H,1,2,4-Triazole 70.4 Solvent rec (DMF) 181.7

Potassium carbonate 105.7 Solvent rec (Tol) 153.3

Dimethyl formamide 186.7 Aq. Effluent 324.3



Water 186.7


Stage-02 Int-A


Triazole derivative 95.8 ITR-INT-A 101.5

Triethyl amine 40.2 Solvent rec (MDC) 187.0

Methane sulfonyl chloride 38.3


Activated Carbon 3.8 Spent carbon 7.7




of 177

Stage-01 Int-B











Stage-02 Int-B






Solvent loss 7.0


Stage-03-04 Int-B







n-Butanol 147.8



Stage-05 Int-B





Solvent loss 9.7


Stage-06 Int-B






of 177


Solvent loss 9.4


Stage-07 Int-B


Stage-VI 92.9 ITR-INT-B 78.0

Hydrobromic acid 961.9 Hydrobromic acid rec 935.5

Soda ash 86.7 Aq. Effluent 476.6



Stage-01 Intraconazole


ITR-INT-A 101.5 IT-I 125.0

ITR-INT-B 78.0 Solvent Rec (DMF) 578.0

Water 287.5 Aq. Effluent 380.5

N,N-Dimethyl formamide 590 Residue 13.5

Potessium Hydroxide 52 Solvent loss 12.0


Stage-02 Itraconazole


IT-I 125.0 Intraconazole 85.00

Toluene 165.0 Solvent Rec (Toluene) 160

Ethyle Acetate 432.0 Solvent Rec (EA) 420

Methanol 695.9 Solvent Rec (Methanol) 675


HyflowSupercell 6.7 Spent Carbon 4.6

Spent Hyflow 10.3

Solvent Loss 37.9


of 177

48. Cetirizine Dihydrochloride


Stage-I:

The 4-Chloro benzhydeylpiperazine react with 2-chloroethanol in presence of Triethylamine

in toluene solvent. After reaction completion toluene was distilled under reduced pressure

and added acetone and passed dry hydrogen chloride gas to isolate 4-Chloro

benzhydrylpiperazineethoxy hydrochloride.

Stage-II:

The 4-Chloro benzhydrylpiperazineethoxycompound react with Sodium monochloro acetate

in presence of Potassium hydroxide in Dimethylformamide. After completion of reaction by

adding water and adjust pH to 9.0 and extract with toluene. Again the aqueous layer is

adjusted to pH 4.0 using Hydrogen chloride and the product is extracted with Methylene

Dichloride. Distilled Methylene Dichloride, added acetone and passed dry Hydrogen chloride

gas to isolate Cetirizine Dihydrochloride.

Route of Synthesis:

of 177

Mass Balance:

Stage-I


4-Chloro benzhydeylpiperazine 230 Stage-I 240

Toluene 800 Recovery Toluene 752

2-Chloroethanol 115 Recovery Triethylamine 232

Triethylamine 250 Loss of Toluene 48

Sodium carbonate 100 Less of Triethylamine 18

Purified water 2300 Effluent 2448.25

Residue 25.32

Carbon dioxide 31.43


Stage-II



Sodium monochloro acetate 175 Recovery Toluene 1175

Potassium hydroxide 85 Recovery Methylene dichloride 690

Dimethylformamide 50 Recovery Acetone 697

Toluene 1250 Loss of Toluene 75

Methylene dichloride 750 Loss of Methylene dichloride 60

Acetone 750 Loss of Acetone 53

Hydrogen chloride 130 Effluent 2073.27

Activated carbon 38 Residue 85.13

Purified water 750 Hydrogen chloride gas 21.6

Activated carbon 38


of 177

49. Rebeprazol Sodium


Stage-1:

2, 3-Lutidine is reacted with Hydrogen Peroxide in presence of Acetic Acid to give N- Oxide

it further reacts with Nitration mixture (Nitric Acid + Sulfuric Acid) to give Stage-1.

Stage-2:

Stage-1 is reacted with 3-Methoxy-1-Propanol and Sodium Hydroxide to get Stage-2

Compound

Stage-3:

Stage-2 Compound is reacted with Acetic Anhydride, Sodium Hydroxide and

Hydrochloric Acid to get Stage-3 Compound

Stage-4:

Stage-3 Compound is reacted with Thionyl Chloride in the presence of MDC Solvent media

to get Stage-4 compound

Stage-5:

Stage-4 Compound is reacted with 2-Mercapto Benzimidazole, Sodium hydroxide in the

presence of Toluene Solvent Media to get Stage-5 Compound

Stage-6:

Stage-5 Compound is reacted with Sodium Hypochlorite to get Rabeprazole Base

Stage-7:

Rabeprazole Base is reacted with Sodium hydroxide to get Rabeprazole Sodium

Route of Synthesis:

of 177

of 177

Mass Balance:

STAGE-1


2,3 Lutidine 46.00 Stage-1 65.00

Acetic acid 46.00 Spent acid 140.00

Hydrogen peroxide 33.00 Effluent 400.80

Nitric acid 30.00 Organic Residue 7.20

Sulfuric acid 108.00

Water 350.00


STAGE-2


Stage-1 65.00 Stage-2 80.00

3-Methoxy-1 –propanol

Acetic anhydride

40.00 Toluene Reco 235.00

Sodium hydroxide 18.50 DMSO Reco 188.00


DMSO 200.00 Inorganic solid waste 29.70

Organic waste 11.80

Water generate 7.00


STAGE-3


Stage-2 80.00 Stage-3 90.00

Acetic anhydride 150.00 Toluene Reco 660.00

NaOH 20.00 Acetic anhydride Reco 107.00

HCL 20.00 Effluent 360.50

Toluene 700.00 Organic Residue 13.50

Water 300.00 Process loss 39.00

Total 1230.00 Total 1230.00

STAGE-4


Stage-3 90.00 Stage-4 80.00

Thionyl chloride 53.00 MDC Reco 710.00

Sodium sulphate 10.00 Solvent loss 37.00

Water 500.00 Organic waste 10.00

MDC 750.00 Organic Residue 16.30

Process loss 23.20

Total 1403.00 Total 1403.00

of 177

STAGE-5


Stage-4 80.00 Stage-5 100.00

2-mercapto benzimidazole 53.00 Toluene Rec. 375.00

Sodium Hydroxide 15.00 Solvent Loss 20.00

Toluene 400.00 Effluent 329.70



STAGE-6


Stage-5 100.00 Stage-6 100.00

Sodium hypochlorite (8%) 327.00 MDC Rec. 570.00

MDC 600.00 Acetone Rec. 137.00

Acetone 150.00 Effluent 944.30

Sodium Hydro Sulphate 12.00 Organic Waste 7.70

MMA in Methanol 10.00 Solvent Loss 40.00

Water 600.00

Total 1799.00 Total 1799.00

STAGE-7


Stage-6 100.00 Rabeprazole Sodium 100.00

Sodium hydroxide 13.00 IPA Rec. 280.00

Isopropyl Alcohol 300.00 Solvent Loss 15.00

Activated Carbon 10.00 Generated Water 5.00

Spent Carbon 10.00

Organic Residue 13.00


of 177

50. Pranlukast


Stage-1:

To a stirred solution of Dimethyl Formamide and Methylene dichloride is added 4-(4-

phenylbutoxy)benzoic acid. Charge drop wise thionyl chloride. After completion, distil out

Methylene Dichloride under vacuum. Charge this reaction mass to stirred solution of 3-

amino 2-hydroxy acetophenone in Methylene dichloride and pyridine at 0-5°C. After

completion of reaction, charge Hydrochloric acid and separate layers. Wash with Sodium

bicarbonate solution and evaporate organic layer to yield N-(2-hydroxy-3- (3-oxo-3-(1H-

tetrazol-5-yl) propanoyl)phenyl)- 4 - (4-phenylbutoxy) benzamide.

Stage-2:

N-(2-hydroxy- 3- (3-oxo- 3-(1H-tetrazol-5-yl) propanoyl) phenyl)-4-(4-phenylbutoxy)

benzamide and sulfuric acid were charged in reactor. Reaction mass was heated at 80° C for

2-3 hours. After completion, reaction mass was quenched in ice water to yield crude

product.

Stage-3:

Pranlukast (crude) and ethyl acetate were charged in reactor and refluxed for 1 hour. Upon

cooling at 10°C. Solid slurry was filtered to obtain pure product.

Route of Synthesis:

of 177

Mass Balance:

Stage-1


4-(4-phenylbutoxy)benzoic acid 100.00 Stage -1 125.00


Ethanone

57.60 Methylene Dichloride(Reco) 570.00

Methylene Dichloride(F/R) 588.00 Solvent Loss 18.00

Dimethyl Formamide 5.00 Effluent 769.30

Thionyl Chloride 59.00 Organic Residue 27.10

Pyridine 89.60 Process Emissions(SO2) 19.80


Sodium Bicarbonate 30.00

Water 300.00

Total 1529.20 Total 1529.20

Stage-2


Stage -1 125.00 Stage -2 106.30

Sulfuric Acid 500.00 Effluent 1562.00


Total 1687.00 Total 1687.00

Stage-3


Stage -2 106.30 Stage -3 106.30

Ethyl Acetate (F/R) 900.00 Ethyl Acetate 862.50

Effluent 15.00

Organic Residue 6.3

Total 1006.30 Total 1006.30

of 177

51. Zonisamide


Stage-I:

4-Hydroxycoumarin was reacted with hydroxylamine HCl in presence of potassium acetate

anhydrous in methanol at desired temperature and appropriate condition. Methanol

distillation, basification, dichloromethane washing and later acidification afforded

Zonisamide Stage-I.

Stage-II:

Obtained solid was reacted with complex of chlorosulphonic acid and 1, 4-dioxane in

ethylene dichloride. Quenching and later water removal and later chlorination using

phosphorus oxychloride in toluene and animation using ammonia afforded Zonisamide

Stage-II.

Stage-III:

Purification of Zonisamide Stage-II using acetone, water and activated charcoal afforded

pure Zonisamide.

Route of Synthesis:

of 177

Mass Balance:

STAGE-I


Methanol 153.00 Stage-1 214.00

4Hydroxy Coumarin 195.30 Methanol Reco 137.7

Hydroxylamine hydrochloride 293.00 Methanol loss 15.3

Potassium acetate 413.00 Effluent 1338.30

Sodium hydroxide 20.00 Dry loss 30.00

Methylene Dichloride 490.00 Organic Residue 29.00

Hydrochloric Acid 100.00

Water 600.00

Total 1764.30 Total 1764.30

STAGE-2


Stage-1 214.00 Stage-2 171.00

Ethylene Dichloride 856.00 HCL gas 20.00

1,4 Dioxane 97.00 EDC Reco 770.4

CSA 120.00 Ammonia gas 130.00

Sodium Sulphate 78.00 Toluene reco 270.00

Toluene 300.00 Aq Effluent 1603.40

Phosphorus Oxychloride 20.00 Solvent loss 115.60

Water 1400.00 Dry loss 35.00

Ammonia Gas 130.00

Total 3215.00 Total 3215.00

Stage-3


Zonisamide (Crude) 180.00 zonisamide 125.00

Ethyl Acetate 1445 Ml CF 1454.00

Activated Carbon 7.00 Carbon + Hyflow 25.00

Hyflowsupercell 7.00 Dry In Loss 35.00

Total 1639.00 Total 1639.00

of 177

52. Telmisartan Process description:

Bibenzimidazole&bromomethyl ester is condensed in presence of sodium methoxide in DMF to give Telmi-I (Methyl–[[4-Methyl-4’6(1-methyl-1H benzimidazol-2-yl)-2-propyl-1Hbenzimidazole -1yl] methyl] biphenyl-2-carboxylate).Telmi-I is hydrolyzed using potassium hydroxide in methanol & water mixture to give Telmisartan. Route of Synthesis:

of 177

Material Balance:

Stage-I

Input QTY.(kgs) Output QTY.(kgs)Bibenzimidazole 186.7 (Stage- I) - termi-I 261.4 Bromo methyl ester 187.3 Dimethyl formamide Rec 921.1 Sodium hydroxide 33.1 Acetone Rec 280.3 Dimethyl formamide 969.6 Methanol Rec 18.6

Acetone 295.1 Wastewater Water 1240.9 Water 1240.9

Sodium bromide 63

Organic waste

Dimethyl formamide 9.7

Acetone 3

Methanol 0.2

Organics 63.1


Stage-II

Input QTY.(kgs) Output QTY.(kgs)(Stage- I) - Termi-I 261.4 Telmisartan 222.2 Potassium hydroxide 76.1 Methanol Rec 3141.6 Acetic acid 470.6 Water 2660.1 Methanol 3304.6 Potassium acetate 133 Activated carbon 13.1 Spent carbon 21.9 Celite 8.8 Methanol 46.3 Water 2817 Water 170.8

Organics 33.8

Acetic acid 389.1

Process loss 132.8 Total 3810 Total 3810

of 177

53. Rosuvastatin Calcium


Stage-1:

4-Fluoro-Benzadehyde reacts with 4-Methyl-3-oxo-pentanoic acid ethyl ester in presence of

Base to give Stage-1 as product.

Stage-2:

Stage-1product reacts with S-Methyl isothio urea and 2,3 Dichloro-5,6-dicyano benzo

quinine in presence of HMPA to give stage-2as product.

Stage-3:

Stage-2 product reacts with meta-chloro peroxy benzoic acid to give Stage-4 as product and

Meta chlorob enzoic acid as by-product.

Stage-4

Stage-3 product reacts with methyl amine in presence of Ethanol solvent media to give

Stage-4 as product.

Stage-5

Stage-4 product reacts with Methane sulfonyl chloride in presence of Sodium hydride as

catalyst to give Stage-5 as product.

Stage-6

Stage-5product under goes reduction and oxidation in presence of Hydrogen gas to give

Stage-6 as product.

Stage-7

Stage-6 product reacts with methyl (3R)-3-(tert-butyldimethyl silyloxy)-5-oxo-6- triphenyl

phosphoranyli denehexanoate.

Stage-8

Stage-7 product reacts with Hydrogen fluoride in presence of Aceto nitrile as solvent media

to give Stage-8 as product.

Stage-9

Stage-8 product reacts with Sodium Boro hydride under goes hydrogenation to give Stage-9

as product.

Stage-10

Stage-9 product reacts with Calcium chloride under goes saponification to give Rosuvastatin

Calcium as product.

of 177

Route of Synthesis:

of 177

of 177

Mass Balance:

STAGE-1


4-Fluorobenzaldehyde 52.00 Stage-1 100.00

4-Methyl-3-oxo-pentanoic

acid ethyl ester

66.30 Methanol Recovery 237.00

Potassium hydroxide 23.50 Methanol Loss 12.00

Methyl Iodide 60.00 Effluent water 590.56

Methanol 250.00 Organic Residue 11.24

Water 500.00


STAGE-2


Stage-1 100.00 Stage-2 115.00

S-Methyl isothiourea 35.00 MDC Recovery 474.00

2,3-Dichloro-5,6-

dicyano benzoquinone

85.00 MDC Loss 25.00

HMPA 100.00 HMPA Recovery 94.50

MDC 500.00 HMPA Loss 5.00

Water 300.00 Effluent water 307.81

By-Product 85.75


Total 1120.00 Total 1120.00

STAGE-3


Stage-2 115.00 Stage-3 120.00

Metachloroperoxybenzoicacid 118.68 MDC Recovery 284.50

MDC 300.00 MDC Loss 15.00

Water 500.00 Effluent water 500.50

Metachloro benzoic

acidReuse

107.67


Total 1033.68 Total 1033.68

STAGE-4


Stage-3 120.00 Stage-4 96.00

Methyl amine 10.20 Ethanol Recovery 238.00

Ethanol 250.00 Ethanol Loss 12.00

Methanol 300.00 Methanol Recovery 284.50

Water 300.00 Methanol Loss 15.00

Effluent water 327.23


of 177


STAGE-5


Stage-4 96.00 Stage-5 112.00

Methanesulfonyl chloride 35.00 Di methoxyethane Recovery 285.00

Sodium hydride(60%) 1.00 Di methoxyethane Loss 15.00

Di methoxyethane 300.00 Hydrochloric acid reuse 11.15



STAGE-6


Stage-5 112.00 Stage-6 95.00

Hydrogen 0.56 Toluene Recovery 284.00

DIBAL-H 1.00 Toluene Loss 15.00

Toluene 300.00 Ethanol Recovery 13.04



STAGE-7


Stage-6 95.00 Stage-7 155.00

Methyl(3R)-3-(tert butyl di methyl

silyloxy)-5-oxo-6-

triphenylphosphoranylidenehexa

noate

144.55 N,N-Dimethyl formamide

Recovery

280.00

Triethylamine 15.00 N,N-Dimethyl formamideLoss 15.00

N,N-Dimethyl formamide 300.00 Effluent water 320.00


By-Product 75.22


STAGE-8


Stage-7 155.00 Stage-8 120.00

Hydrogenfluoride 5.10 THF Recovery 237.00

THF 250.00 THF Loss 12.00

Ethyl acetate 300.00 Ethyl acetate Recovery 285.00

Ethyl acetate Loss 15.00

By-Product 34.24



of 177

STAGE-9


Stage-8 120.00 Stage-9 115.00

Hydrogen 0.48 Ethyl acetate Recovery 237.50

Diethyl methoxyborane 20.00 Ethyl acetate Loss 12.00

Sodium borohydride 1.00 THF Recovery 474.50

Ethyl acetate 250.00 THF Loss 25.00

THF 500.00 Sodium Borohydride Residue 1.00



STAGE-10


Stage-9 115.00 Rosuvastatin Calcium 100.00

Calciumchloride 13.00 Toluene Recovery 473.50

Toluene 500.00 Toluene Loss 25.00

Ethyl acetate 500.00 Ethyl acetate Recovery 475.00

Water 250.00 Ethyl acetate Loss 25.00

Effluent water 262.82


Total 1378.00 Total 1378.00

of 177

54. Posaconazole


Stage-I:

4-Hydroxyphenyl-piperazinyl triazolone is added to Sodium hydroxide solution mixture.

Then add (5R,Cis)-toluene-4-sulfonic acid-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-

yl)methyl tetrahydrofuran-3-yl methylester and Ethyl acetate, combine layers and wash with

Sodium chloride solution. Then centrifuge the mass to collect the Stage-I material.

Stage-II:

Add Stage-I material, Add Pd/C then add Hydrochloric acid to the reaction mass.

Hydrogenate the reaction mass adjust pH using Sodium Hydroxide. The wet material charge

again into the reactor and add Acetone. Then centrifuge the mass to collect Stage-II

(Posaconazole (crude)) material.

Stage-III:

Methylene Dichloride and Isopropyl Alcohol is used as a solvent. Filter the mass to remove

the particles. Add Isopropyl Alcohol to the mass and heat the mass. Then cool the reaction

mass and centrifuge the mass to collect the Posaconazole (Pure).

Route of Synthesis:

of 177

of 177

Mass Balance:

Stage-I


4-Hydroxyphenyl-piperazinyl triazolone 14 Stage - I 18

Recovery Ethyl Acetate 130.5

Recovery Dimethyl

Sulfoxide

103.5

Recovery Isopropyl Alcohol 454.5

(5R,Cis)-toluene-4-sulfonic acid-5-(2,4-

difluorophenyl)-5-(1H-1,2,4-triazol-1-

yl)methyl tetrahydrofuran-3-yl

methylester

14

Loss of Ethyl Acetate 9.5

Sodium Hydroxide 2 Loss of Dimethyl Sulfoxide 6.5

Hydrochloric Acid (35%) 2 Loss of Isopropyl Alcohol 25.5

Sodium Chloride 14 Effluent 320.19

Ethyl Acetate 140 Residue 7.81

Dimethyl Sulfoxide 110

Isopropyl Alcohol 480

Purified Water 300


Stage-II


Stage-I 18 Stage – II 11

Hydrogen 0.5 Recovery Methanol 216

Hydrochloric Acid (35%) 6 Recovery Acetone 117

Sodium Hydroxide 7 Recovery Isopropyl Alcohol 150.5

Methanol 230 Loss of Methanol 14

Acetone 190 Loss of Acetone 73

Isopropyl Alcohol 160 Loss of Isopropyl Alcohol 9.5

Palladium Carbon 9 Effluent 731

Purified Water 720 Residue 9.05

Palladium Carbon 9

Process Emission 0.45


of 177

55. Ursodiol


Stage-1: Preparation of Ketolithocholic acid.

KSM (Chenodeoxycholic acid) oxidized using N-Bromosuccinamide in Acetone Water as

solvent atroom temperature to get 7-Ketolithocholic acid crude which is further purified in

Ethyl acetate,methanol, and water to get pure 7-Ketolithocholic acid (Stage-1).

Stage-2: Preparation of Ursodiol Crude

7-Ketolithocholic acid (Stage-1) reduced in presence of Metal Alloy (Ra/ni) in presence of

BasePotassiumtert. Butoxide in IPA to get Ursodiolcrude.

Stage-3: Preparation of UrsodiolTriethyl amine Salt.

Ursodiolcrude, which is salting with Triethyl amine in Acetone, water to get URSO TEA salt.

This TEA salt is desalting with 10% HCl solution to get Ursodiol.

Route of Synthesis:

of 177

Mass Balance:

of 177

ANNEXURE - IV

___________________________________________________________________________

DETAILS OF WATER CONSUMPTION AND WASTEWATER GENERATION

WATER CONSUMPTION & WASTEWATER GENERATION:

• Domestic wastewater (1.2 KL/day) will be treated and disposed in septic tank & soak

pit.

• Low COD & TDS Industrial wastewater (5 KL/day) will be treated in primary ETP and

sent to CETP of M/s. PETL for further treatment & disposal.

• High COD & TDS Industrial wastewater (0.33 KL/day) will be sent to Common Spray

Dryer of M/s. PETL for further treatment & disposal.

Proposed Scenario (KL/Day) Sr.

No.

Category

Water

Consumption

(KL/Day)

Wastewater

Generation

(KL/Day)

1. Industrial

Process 7.0 4.33

Boiler 1.5 0.2

Cooling 1.4 0.2

Washing 0.6 0.6

Total (Industrial) 10.5 5.33

2. Gardening 1.0 NIL

3. Domestic 1.5 1.2

Total 13.0 6.53

of 177

Water Balance Diagram:

4 KL/Day

0.33 KL/Day

(High COD Stream)

Water: 13.0 KL/Day

Domestic:

1.5 KL/Day

Industrial:

10.5 KL/Day

Gardening:

1.0 KL/Day

Process:

4.33 KL/Day

Boiler:

1.5 KL/Day

Cooling:

1.4 KL/Day

Washing:

0.6 KL/Day Process:

7.0 KL/Day

ETP: 5 KL/Day

Cooling:

0.2 KL/Day

Washing:

0.6 KL/Day

Septic Tank /

Soak pit:

1.2 KL/Day

Boiler:

0.2 KL/Day

CETP

(M/s. PETL)

Common Spray

Dryer (M/s. PETL)

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ANNEXURE - V

___________________________________________________________________________

DETAILS OF EFFLUENT TREATMENT PLANT (ETP)

PROCESS DESCRIPTION OF EFFLUENT TREATMENT PLANT:

First all non-toxic and biodegradable streams of wastewater shall be collected in

Equalization cum Neutralization Tank (ENT-01) where the continuous addition and stirring of

Lime solution is done to maintain neutral pH of wastewater from Lime Dosing Tank (LDT-01)

as per requirement by gravity. Pipe grid is provided at bottom of the ENT-01 to keep all

suspended solids in suspension and to provide proper mixing by air supplied through air

blowers (B-01).

Then after, neutralized wastewater shall be pumped to Flash Mixer (FM-01). Alum and

Polyelectrolyte shall be dosed from Alum Dosing Tank (ADT-01) and Polyelectrolyte Dosing

Tank (PEDT-1) respectively by gravity into FM-01 to carry out coagulation by using a Flash

Mixer. Then after, coagulated wastewater shall be settled in Primary Settling tank (PST-01).

Clear supernatant from PST-01 shall be collected in Intermediate Sump (IS-01).

Treated effluent from IS-01 then passed through Dual Media Filter (DMF-01) to remove

remaining SS from effluent. Then clear Water shall be collected in treated effluent Sump

(TES-01) before sent to common effluent treatment plant for further treatment & disposal.

Sludge settled in PST-01 shall be sent to Sludge Drying Beds (SDBs-A/B) where, dewatering

shall be carried out before storage in HWSA and ultimate disposal to TSDF. Leachate from

SDBs-A/B shall be pumped back to ENT-01 for further treatment.

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SIZE OF TANKS

S.N. Name of unit Size (m x m x m) No. MOC/ Remark

Flow = 5 KLD

1 Equalization cum Neutralization

Tank (ENT-01) 1.6 x 1.6 x 2.0 1 RCC M25

2 Flash Mixer (FM-01) 0.8x 0.8 x 1.5 LD 1 MSFRP

3 Primary Settling Tank(PST-01) 1.5 x 1.0 x 1.2 1 MSFRP

4 Intermediate Sump (IS-01) 1.5 x 1.0 x 1.2 1 MSFRP

5 Dual Media Filter (DMF-01) 300 lit/hr 1 FRP

6 Treated Effluent Sump (TES-01) 2.5 x 2.0 x 2.0 1 RCC M25

7 Lime Dosing Tank (LDT-01) 250 lit 1 HDPE

8 Alum Dosing Tank (ADT-01) 250 lit 1 HDPE

9 Poly Dosing Tank (PDT-01) 100 lit 1 HDPE

10 Sludge Drying Beds (SDBs-A/B) 2.0 x 3.0 2

Bk. Mas. With

PCC Bedding+

filling Media

RCC M25 = REINFORCED CEMENT CONCRETE (M 25 GRADE)

PCC = PLAIN CEMENT CONCRETE

HDPE = HIGH DENSITY POLY ETHELINE

BK.MAS. = BRICK MASONARY

EXPECTED CHARACTERISTICS OF WASTEWATER BEFORE & AFTER TREATMENT

Characteristics (mg/L) Sr.

No.

Parameter

Untreated Treated

CETP Inlet Norms

(mg/L)

1. pH 3-9 6.5-8.5 6.5-8.5

2. SS 150 70 100

3. COD 3000 2500 3000

4. BOD3 1000 800 1200

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Flow Diagram of Effluent Treatment Plant:

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ANNEXURE - VI

___________________________________________________________________________

DETAILS OF AIR POLLUTION CONTROL SYSTEM

Flue Gas Emission:

The flue gas emission through stack attached to IBR Boiler, Thermo pack & DG Set shall

conform to the following standards:

Sr.

No.

Process stack

attached to

Height from

ground level

Consumption

of fuel

Air pollution

control system

Expected

Pollutants

1 IBR boiler

(2 TPH)

11 meter Natural Gas =

300 SM3/Day

Adequate Stack

height will be

provided.

2 Thermo pack

(2 Lakhs

Kcal/hr.)

13 meter Natural Gas =

200 SM3/Day

Adequate Stack

height will be

provided.

3 DG Set

(100 KVA)

11 meter Diesel =

50 Liter/Day

Adequate Stack

height will be

provided.

PM = 150 mg/Nm3

SO2 = 100 ppm

NOx = 50 ppm

Process Gas Emission:

The details of process gas emission from reaction vessel are as below:

Sr.

No.

Process stack

attached to

Height from

ground level

Consumption

of fuel

Air pollution

control system

Expected

Pollutants

1 Reaction

Vessel

11 meter -- Two Stage

Scrubber

Cl2 = 9 mg/Nm3

HCl = 20 mg/Nm3

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ANNEXURE - VII

___________________________________________________________________________

DETAILS OF HAZARDOUS WASTE GENERATION, STORAGE & DISPOSAL

Sr.

No.

Type of waste Category Quantity

Disposal Method

1 ETP Sludge 35.1 5

MT/Month

Collection, Storage, Transportation

& Disposal to TSDF site (M/s. BEIL or

M/s. PSWML)

2 Discarded Bags/

Drums/ Carboys

33.1 800

Nos./Month

Collection, Storage, Transportation,

Decontamination and sell to GPCB

authorized vendors

3 Process Residue -- 5

MT/Month

Collection, Storage, Transportation

& sent to cement industries for co-

processing or sent to CHWIF for

incineration.

4 Used oil 5.1 0.075

KL/Month

Collection, Storage, transportation

and disposal by sell to registered

reprocessor

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ANNEXURE - VIII

___________________________________________________________________________

DETAILS OF HAZARDOUS CHEMICALS STORAGE & HANDLING

Sr.

No.

Name of the

Material

Type of

Hazard

Kind of

storage

Max. Qty.

to be stored

(MT)

Storage condition

i.e. Temp., Pressure

1 Acetic Acid Corrosive Drums 4745.50 Keep container in a cool, well-

ventilated area. Keep container

tightly closed

2 Acetic Anhydride

Flammable

Drums

471.00

Keep container in a cool, well-


tightly closed

3 Acetone Corrosive Drums 115385.50 Keep container in a cool, well-


tightly closed

4 Activated carbon Flammable Store in

Bag/

Drums

365.55 Keep container in a cool, well-


tightly closed

5 Aluminium

Chloride

Corrosive Store in

Bag/

Drums

2136.00 Keep container tightly closed.


ventilated area.

6 Ammonia Gas Corrosive Cylinder 520.00 Store in a cool and well

ventilated place

7 Ammonia

Solution

Corrosive Drums 1680.00 Store in a cool and well

ventilated place

8 Sodium Sulphate Corrosive Store in

Bag/

Drums



ventilated area. Hygroscopic

9 Aniline Toxic Drums 170.00 Store in light-resistance

container. Keep container in a

cool, well-ventilated area. Keep

container tightly closed

10 Benzene Sulfonic

Acid

Corrosive Drums 320.00 Keep container tightly closed.


ventilated area.

11 Bromine Corrosive Glass

bottle



ventilated area.

12 Butanol Flammable Drums 515.00 Keep container in a cool, well-


tightly closed

13 Chloro Acetyl

Chloride

Flammable Drums 710.00 Keep container tightly closed.


ventilated area

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14 Caustic lye Corrosive Store in

Bag/

Drums



ventilated area. Hygroscopic

15 Citric acid Corrosive Store in

Bag/

Drums



ventilated area

16 Hydrochloric Acid Corrosive Drums 17169.85 Keep container tightly closed.


ventilated area.

17 Di Methyl

Formamide

Flammable Drums 8935.00 Keep container in a cool, well-


tightly closed

18 Pyridine Corrosive Drums 1792.00 Keep container in a cool, well-


tightly closed

19 Formaldehyde Flammable Drums 351.40 Store away from sources of

heat or ignition, strong alkalis,

acids, combustibles and

oxidizing agents.

20 Hydrogen gas Flammable Cylinder 78.50 Keep away from heat. Keep

away from sources of ignition.

Keep container tightly closed.

Keep in a cool, well-ventilated

place

21 Iso Propyl

Alcohol

Flammable Drums 62347.00 Keep container in a cool, well-


tightly closed

22 Liq Ammonia Corrosive Cylinder 705.00 Store in a cool, well-ventilated

place. Store and use with

adequate ventilation.

23 Liq. Bromine Flammable Store in

Bag/

Drums



ventilated area

24 Methanol Flammable Drums 31851.7 Keep away from heat. Keep




place

25 Nitric acid Corrosive Drums 75.00 Keep container in a cool, well-

ventilated area. Separate from

acids, alkalies, reducing agents

and combustibles.

26 Sodium Nitrite Corrosive Store in

Bag/

Drums

575.00 Keep container in a cool, well-

ventilated area. Separate from

acids, alkalies, reducing agents

27 Succinic Acid Corrosive Store in

Bag/



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Drums place

28 Sulfuric acid Corrosive Drums 10270.00 Keep container tightly closed.


place

29 Tartric Acid Corrosive Store in

Bag/

Drums



ventilated area.

30 Toluene Flammable Drums 53630.00 Keep away from heat, sparks,

and flame. Keep away from

sources of ignition. Keep

container closed

31 Xylene Flammable Drums 240.00 Keep away from heat, sparks,

and flame. Keep away from

sources of ignition. Keep

container closed

32 Iso Propyl

Acetate

Flammable Drums 8655.00 Keep away from heat. Keep




place

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ANNEXURE - IX

_________________________________________________________________________

SOCIO - ECONOMIC IMPACTS

1) Employment Opportunities

The manpower requirement for the proposed expansion project is being expected to

generate some permanent jobs and secondary jobs for the operation and maintenance of

plant. This will increase direct / indirect employment opportunities and ancillary business

development to some extent for the local population.

This phase is expected to create a beneficial impact on the local socio-economic

environment.

2) Industries

Required raw materials and skilled and unskilled laborers will be utilized maximum from the

local area. The increasing industrial activity will boost the commercial and economical status

of the locality, to some extent.

3) Public Health

The company regularly examines, inspects and tests its emission from sources to make sure

that the emission is below the permissible limit. Hence, there will not be any significant

change in the status of sanitation and the community health of the area, as sufficient

measures have been taken and proposed under the EMP.

4) Transportation and Communication

Since the existing factory is having proper linkage for the transport and communication, the

development of this project will not cause any additional impact.

In brief, as a result of the proposed there will be no adverse impact on sanitation,

communication and community health, as sufficient measures have been proposed to be

taken under the EMP. The proposed scenario is not expected to make any significant change

in the existing status of the socio - economic environment of this region.

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ANNEXURE - X

_________________________________________________________________________

PROPOSED TERMS OF REFERENCE FOR EIA STUDIES

1. Project Description

• Justification of project.

• Promoters and their back ground

• Project site location along with site map of 5 km area and site details providing various

industries, surface water bodies, forests etc.

• Project cost

• Project location and Plant layout.

• Existing infrastructure facilities

• Water source and utilization including proposed water balance.

• List of Products & their capacity

• Details of manufacturing process of proposed products

• List of hazardous chemicals

• Mass balance of each product

• Storage and Transportation of raw materials and products.

2. Description of the Environment and Baseline Data Collection

• Micrometeorological data for wind speed, direction, temperature, humidity and rainfall

in 10 km area.

• Existing environmental status Vis a Vis air, water, noise, soil in 10 km area from the

project site.

• Ground water quality at 8 locations within 10 km.

• Complete water balance

3. Socio Economic Data

• Existing socio-economic status, land use pattern and infrastructure facilities available in

the study area were surveyed.

4. Impacts Identification And Mitigatory Measures

• Identification of impacting activities from the proposed project during construction and

operational phase.

• Impact on air and mitigation measures including green belt

• Impact on water environment and mitigation measures

• Soil pollution source and mitigation measures

• Noise generation and control.

• Solid waste quantification and disposal.

• Control of fugitive emissions

5. Environmental Management Plan

• Details of pollution control measures

• Environment management team

• Proposed schedule for environmental monitoring including post project

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6. Risk Assessment

• Objectives, Philosophy and methodology of risk assessment

• Details on storage facilities

• Process safety, transportation, fire fighting systems, safety features and emergency

capabilities to be adopted.

• Identification of hazards

• Consequence analysis

• Recommendations on the basis of risk assessment done

• Disaster Management Plan.

7. Information for Control of Fugitive Emissions

8. Information on Rain Water Harvesting

9. Green Belt Development plan

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ANNEXURE - XI

_________________________________________________________________________

COPY OF PLOT ALLOTMENT LETTER

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ANNEXURE - XII

_________________________________________________________________________

COPY OF GIDC WATER SUPPLY CERTIFICATE

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ANNEXURE - XIII

_________________________________________________________________________

MEMBERSHIP CERTIFICATE OF CETP (M/s. PETL)

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ANNEXURE - XIV

_________________________________________________________________________

MEMBERSHIP CERTIFICATE OF COMMON HAZARDOUS WASTE DISPOSAL FACILITY &

COMMON INCINERATION FACILITY (M/s. BEIL)

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ANNEXURE - XV

_________________________________________________________________________

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