Oxycodone Synthesis
3
Oxycodone O CH 3 O O H N HO 14-hydroxydihydrocodeinone Oxycodone HCl • Oxynorm® - Nppp o Tablets • Oxycontin® - Napp o Tablets Oxycodone terephthalate Endodan® - (US only) Tablets O CH 3 O O H N HO oxycodone terephthalate COO − COO − H + 2
Transcript of Oxycodone Synthesis
Oxycodone
O
CH3O
OH
NHO
14-hydroxydihydrocodeinone Oxycodone HCl
• Oxynorm® - Nppp o Tablets
• Oxycontin® - Napp o Tablets
Oxycodone terephthalate Endodan® - (US only) Tablets
O
CH3O
OH
NHO
oxycodone terephthalate
COO−
COO−H+
2
Oxycodone synthesis
O
CH3O
CH3OH
N
thebaine
O
N
OCH3
OCH3
O O
O
N
OCH3
OCH3
hydrogen peroxide
1,4-addition
hemiketal hydrolysis
HH
OH
OH
O
CH3O
CH3OH
N
OH
HO
H+
− MeOHO
CH3O
HN
HOO
14-hydroxycodeinone90% yield
O
CH3O
HN
HOO
oxycodonem.p. 218-220oC
oxycodone HClm.p. 270-272oC (dec.)
WO Patent 2004108090
H2, 5% Pd/C
30-40 psi,rt, 20h
iPrOH, 0-5oC, 2h,then 45oC, 3h
HCOOH, H2O2, H2O
O
H O O H
EtOHconc HCl in iPrOH
Alternative synthesis of 14-hydroxycodeinone intermediate
O
CH3O
CH3OH
N
thebaine
O
N
OCH3
OCH3
O O
O
N
OCH3
OCH3
mCPBA
1,4-addition
hemiketal hydrolysis
H
O
OH
O
CH3O
CH3OH
N
OH
HO
aq. H+ − MeOH
O
CH3O
HN
HOO
14-hydroxycodeinone
O
Cl O
Cl
mCPBA
AcOH/CF3COOHheat
aq. H+
ClOH
O
−
O
N
OCH3
OCH3
OH
OH
J. Med. Chem., 1974, 17, 1117
