DYNAMIC RESOLUTION OF ISOMERS AND RESOLVED ISOMERS

• Main Authors: RANDAZZO, MICHAEL E, ROSSO, VICTOR W, HENNINGS, DAVID D, ZHU, JINGYANG, CHEN, JASON G, VENIT, JOHN J, DISCORDIA, ROBERT P, KIAU, SUSANNE, OKUNIEWICZ, FRANCIS J, MADDING, GARY D, KOTNIS, ATUL S
• Format: Patent
• Language: English; French
• Published: 11.04.2002
• Edition: 7
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; APPARATUS THEREFOR; CHEMISTRY; GENERAL METHODS OF ORGANIC CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES

Provided is a dynamic resolution method of enriching a desired isomer of an alpha-substituted carboxylic acid relative to an undesired isomer, the metho d 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 homochir al 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 wit h 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.