A synthesis of 1-azabicyclo[2.2.1]heptane-3-carboxylic acid esters in enantiomerically pure form

Abstract

A novel synthesis of ethyl 1-azabicyclo[2.2.1]heptane-3-carboxylate via 1-benzylperhydropyrano[3,4-c]pyrrol-4-one and 1-benzyl-3-(2-bromoethyl)-4-ethoxycarbonylpyrrolidinium bromide is described. Modification of the method, by incorporation of a chiral substituted benzyl group on the nitrogen atom, has led to the first reported process for the preparation of these esters in enantiomerically pure form. The absolute configuration of the bicyclic esters was deduced by X-ray crystallography of an intermediate, 2-[(S)-1-phenylethyl]perhydropyrano[3,4-c]pyrrole-4-one.