Synthesis of Ketamine Metabolites I and II and Some Anomalous Reactions of 6-Bromoketamine

Article abstract of DOI:10.1021/jo00338a001

Two metabolites of the drug ketamine, 2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride (1), have been synthesized.They are the N-demethyl compound, metabolite I (13), and the N-demethyl-5,6-dehydro analogue, metabolite II (15).Three bromo ketone derived from ketamine have also been synthesized and their realtive configuration assigned.In addition, attempted dehydrohalogenation of axial 2-bromoketamine (2a) with sodium amide in liquid ammonia has produced a novel entry into the 6-azabicyclo<3.2.0>heptane ring system.The structure of the rearrangement product (3) has been confirmed by unequivocal synthesis.Other unusual reactions include the reduction of an N-alkylazetidinone to an N-alkylazetidine and an acid-catalyzed N-alkyl cleavage of a β-lactam.