Method for preparing chiral beta-amino arylbutyric acid derivatives

Abstract

The invention relates to a method for preparing chiral beta-amino arylbutyric acid derivatives (as shown in a structural formula I). The method comprises the following steps: condensing aryl acetoacetic ester with chiral alkamine; carrying out asymmetric induction reduction so as to obtain annular chiral beta-amino arylbutyric acid derivatives (as shown in a structural formula II); and hydrogenating the compound II so as to prepare chiral beta-amino arylbutyric acid derivatives (as shown in the structural formula I). The method is convenient for operation, low in cost and suitable for large-scale production, and the optical purity of the obtained product is high (more than 99.0% ee (enantiomeric excess)).

Description

technical field The invention relates to a method for preparing high optical purity β-aminoaryl butyric acid derivatives (structural formula I) by a chiral induction method, in particular to a chiral drug intermediate β-amino-2,4,5-trifluorobenzenebutadiene Method for the preparation of methyl esters. Background technique Chiral β-aminoaryl butyric acid derivatives are an important class of chiral drug intermediates. The effective synthesis of such chiral intermediates has attracted widespread attention in the pharmaceutical industry. The preparation of chiral β-aminoaryl butyric acid derivatives The method of compound can be roughly divided into three categories: homogeneous asymmetric hydrogenation reduction method, chiral induced reduction method and chiral resolution method. Regarding the homogeneous asymmetric hydrogenation reduction method, references: JACS, 1987, 5856 and OPRD, 2005, 634 reported the reduction of ethyl trifluorophenylacetoacetate with homogeneous chi...

AI Technical Summary

Problems solved by technology

Although there are many reports in the literature on the preparation of homogeneous catalyzed asymmetric hydrogenation, the results are still unsatisfactory. First of all, the chiral ligands and the precious metals used are relatively expensive, and most of them cannot be recycled, so that the target product can be prepared by this method. The cost is high. Secondly, the reaction conditions of homogeneous asymmetric hydrogenation are harsh, and most of them need to be carried out under strict anaerobic conditions. The operation is cumbersome and the repeatability is poor, which brings difficulties to large-scale production. Third, homogeneous The optical purity of asymmetric hydrogenation is greatly affected by the substrate and chiral ligands, and the product usually requires multiple recrystallizations to meet the optical purity requirements

Chiral resolution is an effective method to prepare optically pure target products. However, the yield of the target product is generally low when using the resolution method, and the other half of the compounds cannot be used and are discarded, which affects production costs and environmental protection. have a negative impact

The use of chiral auxiliary group induction is another common and effective method for chiral synthesis. At present, the optical purity of chiral β-aminoaryl butyric acid derivatives induced by existing chiral amines and chiral aminoamides is still low. Too ideal, the product needs to be recrystallized to improve its optical purity, making it difficult to achieve industrial production