Oxycodone → (4R,4aS,12bS)-4a-hydroxy-9-methoxy-3-methyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
Reaction equation
[CH3:1][N:2]1[C@@H:19]2[CH2:20][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([CH2:16][CH2:17][C@:18]2([OH:21])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:15].CN1[C@@H]2CC3C=CC(OC)=C4O[C@H]5C(OC)=CC=C2[C@]5(C=34)CC1>C(O)=O.OO.N.C(O)(=O)C.[Pd]>[CH3:1][N:2]1[C@@H:19]2[CH2:20][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][CH:13]5[C:14]([CH:16]=[CH:17][C@:18]2([OH:21])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:15]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 5
Procedure
Oxycodone may be prepared from thebaine by: dissolution of the thebaine in aqueous formic acid, oxidation treatment with 30% hydrogen peroxide (Seki, 18 Chem. Pharm. Bull. 671-676, 1970), neutralization with aqueous ammonia to yield 14-hydroxycodeinone and hydrogenation of the 14-hydroxycodeinone in acetic acid with the aid of a palladium-charcoal catalyst (Remington's Pharmaceutical Sciences 1041, 1975). Oxidation of thebaine may alternatively be performed using potassium dichromate in acetic acid (Freund et al., 94 J. Prakt. Chem. 135, 1916) or performic acid (Iljima et al., 60 Helv. Chim. Acta 2135-2137, 1977). Improved yield, however, has been reported to be obtained by oxidizing with m-chloroperbenzoic acid in an acetic acid-trifluoroacetic acid mixture (Hauser et al., 17 J. Med. Chem. 1117, 1974; See also, U.S. Pat. No. 4,795,813 to Schwartz, Col. 1, Lines 22-26). Yield may also be improved by hydrogenation of 14-hydroxycodeinone under a pressure of about 30 psi (Kraβnig et al. 329 Arch. Pharm. Pharm. Med. Chem. 325-326, 1996).
Sources & evidence
- ORD record
- ord-85c67cda6ffe413080ae8486a31952ef
- Source dataset
- uspto-grants-2001_07
- Patent number
- US06262266B1
Reaction notes
Loading…