Patent ID: 7388098
Filing Date: 2008-06-17
Classification: C07C,C07D

Abstract:
1. A dynamic resolution method of enriching a desired isomer of a racemic alpha-substituted carboxylic acid relative to an undesired isomer, the method comprising: 1) in a solvent, contacting the racemic alpha-substituted carboxylic acid, wherein the alpha substitution is with a leaving group which is selected from the group consisting of a chloride, a bromide, an iodide, an alkanoate, a benzoate, a thioalkanoate, a thiobenzoate, a thiolate, a silyl alcoholate, an azide and a cyanide, 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; 2) reacting under the selected reaction conditions the salt from step 1) with a nucleophile which is an anion salt selected from the group consisting of a chloride, a bromide, an iodide, an alkanoate, a benzoate, a thioalkanoate, a thiobenzoate, a thiolate, a silyl alcoholate, an azide and a cyanide, 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 reaction conditions are selected to (a) promote nucleophilic substitution of the nucleophile and the leaving group or (b) to produce the increase in the less soluble amine salt in the absence of a strong base; and 3) maintaining the reaction to increase the amount of the desired alpha-substituted carboxylic acid isomer.