Process for the preparation of(R)-2-bromo-3-phenyl -propionic acid

Abstract

Process for the preparation of (R)-2-bromo-3-phenylpropionic acid starting from D-phenylalanine, sodium nitrite and HBr in an aqueous solution, the reaction being carried out in the presence of a bromide salt, at a temperature between −10 and 30° C. The total amount of HBr plus bromide salt lies between 3 and 10 equivalents, calculated relative to the amount of D-phenylalanine, preferably between 4 and 8 equivalents, the amount of bromide salt ranging from 0.5 to 7 equivalents, calculated relative to the amount of D-phenylalanine. The bromide salt is preferably formed in situ from HBr and a base, for instance KOH or NaOH. Preferably, the (R)-2-bromo-3-phenylpropionic acid obtained is subsequently converted into (S)-2-acetylthio-3-phenylpropionic acid using thioacetic acid and an organic base, for instance triethylamine. The (S)-2-acetylthio-3-phenylpropionic acid obtained can be converted into a pharmaceutical, in particular an ACE inhibitor, for instance Omapatrilat.

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