Convenient Method for Synthesis of l-Methamphetamine

Abstract

Enantioselective analysis of methamphetamine (MA) and amphetamine (AP) is necessary in forensic drug analysis. In general, standard materials are required for performing forensic investigation and also for developing new analytical methods. However, l-MA is not commercially available in Japan and only a few reports are available on the enantioselective synthesis of l-MA. We developed a new and convenient method for the synthesis of l-MA using d-norephedrine (d-NE) as a starting material. d-NE was treated with 1,1′-carbonyldiimidazole to produce the corresponding cyclic carbonate, and the product was treated with sodium hydride and iodomethane to form mono-N-methylated amine derivative, which was treated with palladium on activated carbon in hydrogen atmosphere for catalytic reduction. After the addition of aqueous hydrogen chloride (HCl), l-MA was obtained as its HCl salt (total yield 58%).