Synthesis of Terfenadine Carboxylate

Abstract

Abstract A synthesis of terfenadine carboxylate, 1, a metabolite of terfenadine 2, is described. In the key step, the sodium salt of 2-(4-bromophenyl)-2-methylpropionic acid, 7, was lithiated via a metal-halogen exchange using t-BuLi and subsequently condensed with 4-[4-(hydroxydiphenylmethylpiperidin-1-yl]butyraldehyde, 5, to afford terfenadine carboxylate, 1.