N-demethylation of N-methyl alkaloids with ferrocene.
Under Polonovski-type conditions, ferrocene has been found to be a convenient and efficient catalyst for the N-demethylation of a number of N-methyl alkaloids such as opiates and tropanes. By judicious choice of solvent, good yields have been obtained for dextromethorphan, codeine methyl ether, and thebaine. The current methodology is also successful for the N-demethylation of morphine, oripavine, and tropane alkaloids, producing the corresponding N-nor compounds in reasonable yields. Key pharmaceutical intermediates such oxycodone and oxymorphone are also readily N-demethylated using this approach.
Kok
Gaik B
GB
Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Vic. 3052, Australia.
Scammells
Peter J
PJ
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D005296:Ferrous Compounds / Q000737:chemistry*; D000075163:Metallocenes; D008745:Methylation; D009020:Morphine / Q000737:chemistry; D013797:Thebaine / Q000031:analogs & derivatives / Q000737:chemistry
D000470:Alkaloids; D005296:Ferrous Compounds; D000075163:Metallocenes; D013797:Thebaine; C005283:oripavine; D009020:Morphine; C004998:ferrocene