Methanol → (S)-2-(4-Fluorophenyl)-3-methylbutyric acid

Participants

Reaction Steps

Rhodium-catalyzed hydrogenation. -- A catalyst solution was prepared in a glove box (O2 content <1 ppm) by dissolving 0.01045 g (0.0257 mmol) of [Rh(COD)2 ]BF4 and 0.01861 g (0.0257 mmol) of (R,S)-BPPFA-EPIP in 20 ml of tetrahydrofuran and stirring at RT for 15 minutes. Then, 5.0 g (25.75 mmol) of 2-(p-fluorophenyl)-3-methylcrotonic acid, 13 ml of methanol and 33 ml of tetrahydrofuran were placed in a 185 ml autoclave and the catalyst solution prepared above was added. The autoclave was sealed and the hydrogenation was carried out at 20° while stirring and under a constant pressure of 50 bar. The conversion was 100% after 24 hours. The hydrogenation solution was evaporated at 50°/200 mbar and the residue was distilled at 108-110°/0.01 mbar. There were obtained 4.8 g (97%) of (S)-2-(p-fluorophenyl)-3-methylbutyric acid as a colorless oil which solidified at RT; 98.2% ee.

Provenance & Evidence