Development of an enantioselective hydrogenation based synthesis of a glucokinase activator

…, TM Braden, JY Buser, AC DeBaillie…

Index: Magnus, Nicholas A.; Braden, Timothy M.; Buser, Jonas Y.; Debaillie, Amy C.; Heath, Perry C.; Ley, Christopher P.; Remacle, Jacob R.; Varie, David L.; Wilson, Thomas M. Organic Process Research and Development, 2012 , vol. 16, # 5 p. 830 - 835

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Citation Number: 10

Abstract

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 ...