Two-step iron(0)-mediated N-demethylation of N-methyl alkaloids.
A mild and simple two-step Fe(0)-mediated N-demethylation of a number of tertiary N-methyl alkaloids is described. The tertiary N-methylamine is first oxidized to the corresponding N-oxide, which is isolated as the hydrochloride salt. Subsequent treatment of the N-oxide hydrochloride with iron powder readily provides the N-demethylated amine. Representative substrates include a number of opiate and tropane alkaloids. Key intermediates in the synthesis of semisynthetic 14-hydroxy pharmaceutical opiates such as oxycodone and oxymorphone are also readily N-demethylated using this method.
Kok
Gaik B
GB
Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia.
Pye
Cory C
CC
Singer
Robert D
RD
Scammells
Peter J
PJ
D000470:Alkaloids / Q000737:chemistry*; D007501:Iron / Q000737:chemistry*; D008744:Methylamines / Q000737:chemistry*; D008745:Methylation; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000737:chemistry*; D010084:Oxidation-Reduction
D000470:Alkaloids; D008744:Methylamines; D009589:Nitrogen Oxides; D007501:Iron