Method for synthesizing (S)-isopropyl-(2-piperidine) phenyl-methylhistamine

Abstract

A process for synthesizing (S)-isopropyl-(2-pipeeridine) phenyl-methylamine nicludes reaction between trimethylallyl boronane and tartaric acid derivative, asymmetric allylation reaction on o-chlorobenzaldehyde, halogenation, reacting on azo compound, catalytic reduction reaction and coupling with piperidine.

Description

technical field [0001] The invention relates to a synthesis method of (S)-isopropyl-(2-piperidine)phenyl-methylamine. Background technique [0002] Repaglinide is a new type of non-sulfonylurea insulin secretagogue, used as an adjuvant drug for diet therapy and exercise as monotherapy, and can be used as a first-line treatment drug for type II diabetes. (S)-Isopropyl-(2-piperidine)phenyl-methylamine is an important intermediate in the synthesis of repaglinide. [0003] A few representative routes are as follows: [0004] 1. In 1998, Grell et al. (J.Med.Chem.1998, 41, 5219) reported several synthetic methods of repaglinide intermediates, among them, chiral synthesis controlled by chiral prosthetic groups (1-2) , Catalyzed asymmetric synthesis (3) and kinetic resolution (4). [0005] [0006] [0007] The chiral prosthetic groups used in routes 1 and 2 are expensive, cannot be recycled, and the synthesis cost is high; the source of raw materials for route 3 is not eas...

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Problems solved by technology

[0010] The total yield of this route is only 28.3%, and the product is a racemic mixture, which requires chiral resolution

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