Novel chemical resolution method for 3-hydroxy-3-phenylpropanoic acid compounds

Abstract

The invention discloses a novel chemical resolution method for 3-hydroxy-3-phenylpropanoic acid compounds. The method comprises the following steps: (1) 1 kg of 3-hydroxy-3-phenylpropanoic acid (racemate) and 5 L of ethyl acetate are added to a reaction flask, phenethylamine is added, reflux reaction is performed for 1 h, temperature is reduced to 0-10 DEG C for crystallization for 1 h, and a filter cake obtained after filtering is washed with 500 mL of ethyl acetate; (2) the final product in step (1) is added to the reaction flask, and 5 L of 2N hydrochloric acid and 5 L of ethyl acetate areadded; (3) a product is stirred by keeping temperature at 20-30 DEG C for 30 min and left to stand for layering, aqueous phase is extracted with 2 L of ethyl acetate, organic phase is mixed, washed with 5 L of water and 5 L of 10% sodium chloride and condensed under reduced pressure, 3-hydroxy-3-phenylpropanoic acid is obtained, ee is higher than 99%, and yield is higher than 43%. The method can be applied to industrial production and has the advantages of simple operation and low cost.

Description

technical field [0001] The invention relates to the technical field of chiral compound analysis, in particular to a novel chemical resolution method for 3-hydroxy-3-phenylpropionic acid compounds. Background technique [0002] Chiral compounds cannot be resolved by conventional analysis and preparation methods, and an asymmetric (chiral) environment needs to be introduced. There are many methods for enantiomer resolution, which can be mainly divided into two categories. Non-chromatographic and chromatographic methods. Generally speaking, no matter which method is used for separation, the basic principle is mostly based on the conversion of a mixture of enantiomers into diastereoisomers, and then using their differences in chemical or physicochemical properties to separate them, non-chromatographic methods and a brief introduction to chromatography is as follows: [0003] 1. Liquid chromatography method: Introduce a chiral selective agent into the mobile phase or bond the ...

AI Technical Summary

Problems solved by technology

However, the preparation of chiral stationary phase is difficult, and the versatility of the chiral column is poor, and the test sample sometimes needs to be derivatized before the column, which leads to high cost, limited production scale, and poor product quality.