title: Two-step iron(0)-mediated N-demethylation of N-methyl alkaloids.
abstract: 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.
authors.affiliation: Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia.
authors.forename: Gaik B
authors.initials: GB
authors.lastname: Kok
authors.forename: Cory C
authors.initials: CC
authors.lastname: Pye
authors.forename: Robert D
authors.initials: RD
authors.lastname: Singer
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Scammells
mesh_terms: 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
chemical_list: D000470:Alkaloids; D008744:Methylamines; D009589:Nitrogen Oxides; D007501:Iron