Synthesis of thebaine and oripavine from codeine and morphine.
A practical synthesis of thebaine and oripavine has been developed from codeine and morphine, respectively. Attempts to use a codeinone intermediate gave poor yields; however, methylation of the potassium salt of codeine to give codeine methyl ether followed by oxidation with gamma-MnO2 gave thebaine in 67% yield from codeine. Similarly, the potassium salt of the di-O-anion of morphine was selectively alkylated to give morphine 6-methyl ether (heterocodeine) in better than 90% yield. Hetercodeine was then acetylated and oxidized to oripavine 3-acetate which was hydrolyzed to give oripavine in 73% yield from morphine.
D003061:Codeine; D008722:Methods; D008745:Methylation; D009020:Morphine; D010084:Oxidation-Reduction; D013797:Thebaine / Q000031:analogs & derivatives / Q000138:chemical synthesis*
D013797:Thebaine; C005283:oripavine; D009020:Morphine; D003061:Codeine