Preparation of highly enantiopure stereoisomers of 1-(2,6-dimethylphenoxy)-2-aminopropane (mexiletine)

Mexiletine [1-(2,6-dimethylphenoxy)-2-aminopropane], an orally effective an tiarrhythmic agent, exhibits enantioselective pharmacokinetics and pharmaco dynamics during mexiletine therapy. The purpose of this paper is to emphasi ze the advantage of tetrahydropyranyl-protected mandelic acid (THPMA) in th e resolution of mexiletine enantiomers. Both enantiomers of mexiletine were obtained in 99% enantiomeric excess. Judging by the differential shielding effects in the H-1 and C-13 NMR analyses, we have observed the opposite pr edominant conformation for the mexiletine mandelates in comparison with the O-methylmandelates. (C) 1999 Elsevier Science Ltd. All rights reserved.