Optical resolution of N-methylamphetamine via diastereoisomeric salt formation with 2R,3R-O,O?-di-p-toluoyltartaric acid

Abstract

Racemic N-methylamphetamine can be resolved by O,O′-di-p-toluoyltartaric acid in methanol either by the classic Pasteurian method by fractional crystallization of the neutral diastereoisomeric salt pair (molar ratio of the base:acid 2:1) or by the Marckwald or the Pope-Peachey method by fractional crystallization of the enantiomer (or its hydrochloride) from the diastereoisomeric salt (molar ratio of the base:acid 4:1). The optical purity of the precipitated salt could be increased slightly by performing the resolution in a water-water immiscible solvent system (water-dichloroethane). We found that the O,O’-Di-p-toluoyltartaric acid forms exclusively neutral salts with the N-methylamphetamine. This resolution may have practical application because the efficiency of the resolution is in the same range as with tartaric acid but only 0.25 molar equivalent of resolving agent is required for the resolution of 1 mol base. Chirality 11:373–375, 1999. © 1999 Wiley-Liss, Inc.