Citric Acid → (2r,3s)-2-(4-Cyano-3-(trifluoromethyl)phenylamino)-3-hydroxybutanoic acid

Participants

Reaction Conditions

Reaction Steps

4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) (2.0 g, 10.6 mmol) was mixed together with H-D-Thr-OH (1.51 g, 12.69 mmol) in DMSO (30 mL), K2CO3 (3.06 g, 22.21 mmol) was added to the reaction mixture and stirred at 75° C. for 24 h. The reaction mixture was cooled to room temperature and poured slowly into a 10% citric acid solution and stirred for 10 min at room temperature. The solution was extracted with EtOAc several times to get the crude product. The crude product was chromatographed with a gradient of hexanes/EtOAc and then with EtOAc, 100% to get the pure final product (1.7 g): 1H NMR (500 MHz, CDCl3, δ in ppm) 9.02 (br s, 1H), 7.76 (d, J=9 Hz, 1H), 7.52 (s, 1H), 7.39 (d, J=9 Hz, 1H), 6.41d, J=9 Hz, 1H), 4.42 (m, 1H), 4.01 (m, 1H), 1.24 (d, J=6 Hz, 3H).

Provenance & Evidence