A process for the preparation of tert-butyl N-[(1R)-2-[1,1'-biphenyl]-4-yl-1-(hydroxymethyl)ethyl]carbamate

Abstract

The application provides a preparation method of a key intermediate N-[(1R)-2-[1,1'-biphenyl]-4-yl-1-(hydroxymethyl)ethyl] tert-butyl carbamate of a new anti-heart failure drug sacubitril sodium, which comprises the following steps: taking 2-amino-1,3-propanediol Boc derivative compound 1 as a starting raw material, and then performing solidification enzyme catalyzed esterification, cyclization, oxidation, ring-opening reaction and finally hydrolysis to obtain the target product compound 7; the method has the advantages of short route, high efficiency, low price of the starting raw material, avoidance of use of expensive chiral catalysts in the reaction process, great reduction of process cost, low requirement of experimental conditions, simple operation, high yield and suitability for process amplification.

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