Method for enzymatic resolution of phenylethylamines by using novel acyl donor

Abstract

The invention discloses a method for enzymatic resolution of phenethylamines by using a novel acyl donor, which comprises following steps: (1) adding parachlorophenol, organic acid, dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) with a molar ratio of 1:(1-2):(1-2):(0.03-0.05), reacting under stirring, filtering, concentrating and separating by column chromatography to obtain the acyl donor; alternatively adding acetophenone and sodium borohydride with a molar ratio of 1:1.2 into methanol, reacting under stirring, distilled under reduced pressure, water washing, carrying out extraction with dichloromethane, drying and concentrating to obtain phenethyl alcohol, adding phenethyl alcohol, acetyl chloride and triethylamine with a molar ratio of 1:(1-1.2):(1-1.3), reacting under stirring, washing with saturated sodium bicarbonate solution, drying, concentrating and separating by column chromatography to obtain the acyl donor; and (2) adding phenylethylamine and the acyl donor with a molar ratio 1:(0.6-1) into 2-4mL organic solvent, and reacting with 10-20 mg / mL lipase to obtain amide. The method of the invention has advantages of mild reaction conditions, fast reaction, high conversion rate and high optical purity of the product, and has great application value.

Description

field of invention [0001] The invention relates to a dynamic resolution method, in particular to a method for using a novel acyl donor for the dynamic resolution of phenethylamine enzymatic method. Background technique [0002] Various monochiral phenylethylamines are very important chiral synthons, and are indispensable intermediates in the synthesis of medicines, agricultural chemicals, daily necessities, pheromones and high-quality liquid crystals, and are also important in asymmetric synthesis. important chiral auxiliaries. At present, monochiral phenethylamines are mainly obtained by chemical resolution and asymmetric synthesis. However, the former has disadvantages such as many operation steps, low reaction efficiency, poor selectivity, and low yield; the latter uses chiral metal complexes as catalysts, and has disadvantages such as difficult access to chiral reagents and difficulty in recycling. Enzymatic kinetic resolution (Kinetic Resolution, KR) racemate as a gre...

AI Technical Summary

Problems solved by technology

However, the former has disadvantages such as many operation steps, low reaction efficiency, poor selectivity, and low yield; the latter uses chiral metal complexes as catalysts, and there are disadvantages such as chiral reagents are not easy to obtain and recycling is difficult.

Enzymatic kinetic resolution (Kinetic Resolution, KR) racemate as a green synthesis technology is more and more widely used in the preparation of chiral compounds due to its good activity, mild reaction conditions and high stereoselectivity, but There are certain deficiencies in this method: in the resolution process, the donors that adopt are generally vinyl acetate or isopropenyl acetate

During their use, the reaction rate is often slow, and the optical purity of the obtained product is not high, which greatly reduces the application range of the enzymatic kinetic resolution process.

Images