A method for resolution and preparation of optically pure r-2-naphthylethylamine

Abstract

The invention relates to a method for preparing R-2-naphthylethylamine by dynamic kinetic resolution. Using 2-naphthylethylamine as raw material, Novozym 435 as a resolution catalyst, R-1-phenylethyl alcohol acetate as an acyl donor, and Raney nickel as a racemization catalyst, hydrogen is introduced into the autoclave to react, 2- Complete conversion of naphthylethylamine to obtain (R)-(1-(2-naphthyl)ethyl)acetamide (ee value 99%); acid hydrolysis after purification of the amide to obtain R-2-naphthylethylamine salt, which is passed through Operations such as alkalization, extraction, drying, and concentration can obtain R-2-naphthylethylamine, and the product yield and ee value of the whole steps can reach more than 90%. The invention has the characteristics of cheap and easy to obtain racemic catalyst, complete utilization of raw materials, good product yield, high optical purity and the like. In the production and preparation of R-2-naphthylethylamine, it has great guidance and application value.

Description

technical field [0001] The invention relates to a resolution and preparation method of optically pure chiral amine, in particular to a resolution and preparation method of optically pure R-2-naphthylethylamine. Background technique [0002] Optically pure chiral amines are very important pharmaceutical intermediates. At present, optically pure chiral amines are mainly obtained through the following methods: enzymatic resolution (Indian J. Chem. Sect. B 2005, 44, 1312-1316; J. Org. Chem. 1997, 62, 3488-3495); Chemical resolution: resolution with chiral α-hydroxyphenylacetic acid (US6342636; Tetrahedron: asymmetry, 1998, 9, 2219-2212) or protected chiral glycerol derivatives (Tetrahedron: asymmetry, 1996, 7, 1117-1122 ; Tetrahedron: asymmetry, 2002, 13, 2277-2282); obtained by asymmetric synthesis of the corresponding aldehyde (WO2004 / 110976; J. Org. Chem. 1992, 57, 1237-1241). [0003] Among the existing methods, the cost of asymmetric synthesis is high and it is often diff...

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Problems solved by technology

[0003] Among the existing methods, asymmetric synthesis is costly and often difficult to obtain products with high optical purity; chemical resolution and enzymatic kinetic resolution have the disadvantage of low raw material utilization, which is only 50% at most; In the reported enzymatic dynamic kinetic resolution method, the racemization catalysts used are usually complexes of some noble metals such as ruthenium and rhodium. These racemization catalysts are extremely expensive, and when these racemization catalysts are used in the resolution preparation process , although a high conversion rate is achieved, it is difficult to obtain a high optical purity of the product

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