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

Racemic N-methylamphetamine can be resolved by O,O'-di-p-toluoyltartaric ac id in methanol either by the classic Pasteurian method by fractional crysta llization of the neutral diastereoisomeric salt pair (molar ratio of the ba se:acid 2:1) or by the Marckwald or the Pope-Peachey method by fractional c rystallization of the enantiomer (or its hydrochloride) from the diastereoi someric 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 wi th the N-methylamphetamine. This resolution may have practical application because the efficiency of the resolution is in the same range as with tarta ric acid but only 0.25 molar equivalent of resolving agent is required for the resolution of 1 mol base. Chirality 11:373-375, 1999. (C) 1999 Wiley-Li ss, Inc.