Method for preparing R-beta-aminobenzene butyric acid derivative

Abstract

The invention relates to a method for preparing an R-beta-aminobenzene butyric acid derivative (I) serving as a chiral medicament midbody and a pharmaceutically acceptable salt thereof. In the method, chemical synthesis processes including the resolution of a DL body of a beta-aminobenzene butyric acid derivative by using a resolving agent are used to obtain a target matter of a special optical configuration. The preparation method comprises a step of using resolving agents which are di-p-toluoyl-L-tartaric acid and di-p-toluoyl-D-tartaric acid to salify and resolve in an alcohols solvent andan alcohols water solvent. The obtained R-beta-aminobenzene butyric acid derivative (I) has a high optical purity and an accumulated overall yield of the positive and negative resolution of up to over 70 percent. The R-beta-aminobenzene butyric acid derivative (I) prepared by the invention can better applied to synthesizing medicaments.

Description

technical field [0001] The present invention relates to the method for obtaining the R-beta-aminophenylbutyric acid derivative (I) of single optical configuration by chemical synthesis method including resolution method, the formula (I) compound obtained according to the method of the present invention can be used for many Synthesis of chiral drugs. [0002] Background technique [0003] With the development of drug synthesis technology, more and more drugs containing chiral atoms tend to be made into drugs with a single optical configuration. Chiral β-aminophenylbutyric acid derivatives are an important chiral drug Intermediates are commonly reported by methods prepared by chiral catalytic reduction; for example, references: JACS., 1987,5856 describes the method for preparing the above-mentioned target object as a raw material with 2,4,5-trifluorophenylacetoacetate ethyl ester, Reduction with chiral reduction catalyst Ru-(S)-BINAP to obtain chiral β-hydroxy-2,4,5-triflu...

AI Technical Summary

Problems solved by technology

[0004] Although there are many reports on the preparation of chiral β-aminophenylbutyric acid derivatives by chiral reduction method, the results obtained by chiral reduction method are often unsatisfactory.

First of all, the chiral reduction catalyst used in this method is often expensive, which greatly increases the manufacturing cost of the target compound

In practice, although homogeneous catalysis is possible to obtain target compounds with higher optical purity, the recovery of homogeneous catalyzed catalysts is difficult, which often leads to high cost of synthesizing target compounds, making the synthetic route lose the value of industrial production

Secondly, the chiral reduction reaction conditions are harsh, the chiral reduction catalyst itself is not easy to prepare, and the chiral reduction process is relatively cumbersome.

The third is that the selectivity of the chiral reduction catalyst is often low, so the optical purity of the product is not satisfactory, and the product often needs to undergo multiple recrystallization steps to meet the requirements, and it is difficult to achieve industrialized mass production.

[0005] For now, there are no reference materials for the preparation of R-β-aminobenzenebutyric acid derivatives by resolution

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