Preparation method of R-3, 5-bis (trifluoromethyl) phenyl ethanol

Abstract

The invention discloses a preparation method of R-3, 5-bis (trifluoromethyl) phenyl ethanol. According to the preparation method disclosed by the invention, 3, 5-bis (trifluoromethyl) phenyl ethanol is taken as a raw material, chlorophenol acetate is taken as an acyl donor, Novozym435 is taken as a resolution catalyst, acidic resin is taken as a racemic catalyst, and then dynamic kinetic resolution is performed to obtain R-3, 5-bis (trifluoromethyl) phenyl ethanol acetate. Then, ester is hydrolyzed to obtain R-3, 5-bis (trifluoromethyl) phenyl ethanol, the final product yield can be more than 90%, and the ee value of the product is more than 99%. The method is simple to operate, the used racemic catalyst has the characteristics of low price, easiness in obtainment, reusability, high product yield, good optical purity and the like, and the method further has great guide and application values in production and preparation processes of R-3, 5-bis (trifluoromethyl) phenyl ethanol.

Description

technical field [0001] The invention relates to a preparation method of optically pure chiral alcohol, in particular to a preparation method of dynamic dynamic resolution of R-3,5-bistrifluoromethylphenethyl alcohol. Background technique [0002] R-3,5-bistrifluoromethylphenylethanol is an important intermediate for the synthesis of antiemetic drug Aprepitant, as well as an important intermediate for the synthesis of NK1 receptor antagonists and depression drugs. [0003] At present, the methods of R-3,5-bistrifluoromethylphenethyl alcohol reported at home and abroad mainly include biological methods and chemical methods. Among them, the biological method can be divided into the biocatalytic asymmetric synthesis method and the enzyme-catalyzed kinetic resolution method. The biocatalytic asymmetric synthesis method mainly uses the biological enzyme KRED-101 as a catalyst (Practical Methods for Biocatalysis and Biotransformations, null, 2010; 273-275) or the methanol transfe...

AI Technical Summary

Problems solved by technology

The biocatalytic asymmetric synthesis method mainly uses the biological enzyme KRED-101 as a catalyst (Practical Methods for Biocatalysis and Biotransformations, null, 2010; 273-275) or the methanol transfer hydrogen method (Indian Pat Appl, 2005CH01159, 2007-09 -07) Catalyze the asymmetric reduction of R-3,5-bistrifluoromethylacetophenone to R-3,5-bistrifluoromethylphenethyl alcohol, and the enzyme-catalyzed kinetic resolution method utilizes enzyme selectivity Catalytic synthesis of R-3,5-bistrifluoromethylphenethyl alcohol from 3,5-bistrifluoromethylphenethyl alcohol (Progress in Chemical Industry, 2013, 32(11); 2691-2694), these several biocatalytic methods Both have the disadvantage of low product yield

[0004] The chemical synthesis method is to use Ru and other noble metal complexes as catalysts to asymmetrically catalyze the reduction of 3,5-bistrifluoromethylacetophenone to R-3,5-bistrifluoromethylphenethyl alcohol (Organic Process Research & Development, 2007,11(3):519-523; Fine Chemicals, 2013,30(4),468-470), this method has disadvantages such as expensive metal catalyst and low optical purity of the product