A kind of preparation method of biphenylalanine derivative

Abstract

The invention relates to a preparation method of a compound of formula (i). The compound of formula i is prepared by using glycine methyl ester or its hydrochloride as a starting material, through protection of benzaldehyde, alkylation of benzyl chloride, and deprotection. The starting material of the invention is easy to obtain and low in price, and the intermediates involved in the reaction process do not need to be separated and purified, the operation is simple, the reaction conditions are mild, and the method is suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to a preparation method of biphenylalanine derivatives. Background technique [0002] Compounds with the structure of biphenylalanine derivatives are an important class of pharmaceutical intermediates, especially as inhibitors of some enzymes in vivo, such as neprilysin inhibitors, neutral endopeptidase inhibitors, etc. [0003] There are three main methods for preparing biphenylalanine: [0004] 1) Using biphenyl monoformaldehyde and hydantoin as starting materials, biphenylalanine was obtained through condensation, reduction, and hydrolysis (see WO2007083776): [0005] [0006] The disadvantage of this route is that expensive Pd / C is needed in the reduction process, and the reaction conditions are relatively harsh, requiring 10-20 atmospheres, which requires high equipment requirements. [0007] 2) Biphenylalanine derivatives were prepared by condensation, decarboxylation, esterification, reduction, and -Boc protection usin...

AI Technical Summary

Problems solved by technology

[0012] The disadvantage of this route is that it uses expensive and difficult-to-obtain N-(diphenylmethylenyl)aminoacetic acid methyl ester as a raw material, and after hydrolysis, the diphenylmethyl group with a larger molecular weight is removed, and the atom utilization is low, resulting in cost increase

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