The Practical Synthesis of (2S)-7-Methoxy-1, 2, 3, 4-tetrahydro-2-naphthylamine via Optical Resolution of 2-(3-Methoxybenzyl)succinic Acid

Abstract

We describe the practical synthetic route for (2S)-7-methoxy-1, 2, 3, 4-tetrahydro-2-naphthylamine [(2S)-2-amino-7-methoxytetraline; (S)-AMT]. (2R)-2-(3-Methoxybenzyl)succinic acid [(R)-1] was obtained by the optical resolution of 2-(3-methoxybenzyl)succinic acid (1) as the salt of (1R, 2S)-2-(benzylamino)cyclohexylmethanol (7), and (R)-1 was converted to the optically active (2S)-7-methoxy-1, 2, 3, 4-tetrahydro-2-naphthoic acid [(S)-2] by the intramolecular Friedel-Crafts reaction followed by catalytic hydrogenation. (S)-AMT was obtained from the acid (S)-2 by Hofmann rearrangement without racemization.