Development of an Enantioselective Hydrogenation Based Synthesis of a Glucokinase Activator

This article describes the development and optimization of chemical reactions and subsequent multikilogram preparation of the glucokinase activator ( R )- 1 to fund clinical evaluation as a potential therapeutic for type II diabetes. The major process developments presented here are a Wittig olefination isomerization based synthesis of an E -acrylic acid, an optimized enantioselective hydrogenation of the E -acrylic acid, and a challenging final amide coupling.