Bristol-myers Squibb Compnay

Atul S Kotnis

John J Venit

David R Kronenthal

Jollie D Godfrey, Jr

Nachimuthu Soundararajan

Paul Alan Jass

John L Dillon, Jr

Sushil K Srivastava

Keith Ramig

Saibaba Racha

Mark D Schwinden

Gerald L Powers

Victor W Rosso

Jingyang Zhu

Gary D Madding

Jason G Chen

Michael E Randazzo

D David Hennings

Robert P Discordia

Jeffrey Depue

Simon Leung

Eric D Dowdy

Daniel J Watson

Francis J Okuniewicz

Susanne Kiau

Provided is a dynamic resolution method of enriching a desired isomer of an alpha-substituted carboxylic acid relative to an undesired isomer, the method comprising: (a) in a solvent, contacting the alpha-substituted carboxylic acid, wherein the alpha substitution is with a leaving group and wherein the alpha carbon is chiral, with a homochiral amine to form a salt that is partially insoluble under selected reaction conditions, wherein the homochiral amine is selected so that the solubility of the amine salt of the undesired alpha-substituted carboxylic acid is greater than that of the amine salt of the desired alpha-substituted carboxylic acid under the selected reaction conditions; (b) reacting under the selected reaction conditions the salt with a nucleophile, wherein the reacting is effective in producing a net increase in the less soluble amine salt of the alpha-substituted carboxylic acid, and wherein the selected conditions are selected to (i) promote nucleophilic substitution of the nucleophile and the leaving group or (ii) to produce the increase in the less soluble amine salt in the absence of a strong base; and (c) maintaining the reaction for a period of time effective to increase the amount of the desired alpha-substituted carboxylic acid isomer.

Dynamic resolution of isomers and resolved isomers

This invention describes a process for preparing hydroxyazapirones of Formula I from azapirones of Formula II. The process comprises treating azapirones with a strong base, monitoring enolate formation of the azapirone by IR spectroscopy, and reacting the enolate with a source of molecular oxygen in the presence of a reductant. The process is suitable for large scale production of hydroxyazapirones.

Process for hydroxyazapirones

Preparation of (S)-2-amino-6,6-dimethoxyhexanoic acid methyl ester via novel dioxolanes

Preparation of (s)-2-amino-6,6-dimethoxyhexanoic acid methyl ester via novel dioxolanes

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Kendall Park, NJ, United States of America

Atul S Kotnis