Method of using a-substituted benzylamine chiral auxiliary synthetic reagents

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United States Patent and Trademark Office

Abstract

Description

This invention relates to the use of a family of chiral a-substituted benzylamine reagents during chemical synthesis. Specifically, the reagents can be used in an auxiliary manner to deliver either a substituted or unsubstituted nitrogen atom while simultaneously bestowing an asymmetric bias toward the formation and separation of the diastereomeric intermediates that result from reaction of the reagents with racemic substrates also having one or more asymmetric atoms. The chiral auxiliary portion of the reagents can then be readily removed at some later and convenient stage of the overall synthetic scheme. The initial nitrogen-delivery reaction, asymmetric separation procedures, and removal of the chiral auxiliary can all be conducted under routine experimental conditions, including the final debenzylation, such that the overall method is adaptable to large-scale chemistry. Since the reagents are particularly useful whenever a nitrogen-containing system has alpha- , beta- or gamma-asymmetry, the latter being a common structural motif within many pharmaceutical agents, the methods are of primary utility for the laboratory preparation and large-scale manufacture of enantimerically pure drug molecules.

Keywords

564/303, 564/302

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