Efficient synthesis of racemic and enantiomerically pure 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and esters

Article abstract of DOI:10.1055/s-1992-26325

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 1a 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.