Efficient Synthesis of Racemic and Enantiomerically Pure 1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acid and Esters

Abstract

Racemic and optically pure 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids and esters were prepared, via base-catalyzed cyclization of 1,2-bis (halomethyl) benzenes 1 a or b with diethyl 2-(acetylamino)malonate (2), subsequent decarboxylation and amide cleavage. The enantiomer resolution was achieved either by esterification with (-)-menthol followed by column chromatographic separation of the diastereomeric mixture or by diasteromeric salt separation of the benzylic ester with mandelic acid and base- catalyzed saponification of both esters.