Synthesis of the β3-adrenergic receptor agonist solabegron and analogous N-(2-ethylamino)-β-amino alcohols from O-acylated cyanohydrins - expanding the scope of minor enantiomer recycling

Abstract

A novel methodology to produce highly enantioenriched N-(2-ethylamino)-β-amino alcohols was developed. These compounds were obtained from O-(α-bromoacyl) cyanohydrins, which were synthesized by the minor enantiomer methodology employing a Lewis acid and a biocatalyst, followed by nucleophilic substitution with amines and reduction. The importance of the developed methodology was demonstrated by completing a highly enantioselective total synthesis of the β3-adrenergic receptor agonist Solabegron.