Preparation of (R)- and (S)-3-Hydroxy-2-(trifluoromethyl)propionic Acid by Resolution with (R,R)- and (S,S)-2-Amino-1-phenylpropane-1,3-diol

Abstract

Racemic 2-trifluoromethyl-3-hydroxypropionic acid (rac-1) is prepared on a 50 g scale from 3,3,3-trifluoropropene in four steps, the overall yield being 40%. A procedure for the resolution of rac-1 with 2-amino-1-phenylpropane-1,3-diol is described (25 g scale). The acids (R)-1 and (S)-1 are isolated, their enantiomer purities determined by GC analysis of the corresponding methyl esters on a chiral column and their chirality senses assigned from an X-ray crystal structure of the salt formed with phenylethylamine. The non-fluorinated analog of 1 is frequently employed as a chiral synthetic building block ('Roche acid').