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 (<i>R</i>)-<b>1</b> 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 <i>E</i>-acrylic acid, an optimized enantioselective hydrogenation of the <i>E</i>-acrylic acid, and a challenging final amide coupling