Potassium Carbonate → (R)-2-(4-cyano-3-(trifluoromethyl)phenylamino)-3,3-dimethylbutanoic acid

Participants

Reaction Conditions

Reaction Steps

4-fluoro-2-(trifluoromethyl)benzonitrile (7.10 g, 37.55 mmol) was mixed together with (R)-2-amino-3-hydroxy-3-methylbutanoic acid (5 g, 37.55 mmol) in DMSO (220 mL). K2CO3 (15.57 g, 112.65 mmol) was added to the reaction mixture and the reaction mixture stirred at 85° C. for 96 h. The reaction mixture was allowed to cool to room temperature and quenched with H2O (40 mL) and extracted with EtOAc (2×80 mL). The aqueous layer was then acidified with solid citric acid and extracted with EtOAc (2×80 mL). The later organic extracts were combined, washed with H2O (2×30 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provided the title compound as a pale yellow solid (11.1 g, 98%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 7.57 (d, J=9 Hz, 1H), 6.98 (d, J=2 Hz, 1H), 6.80 (dd, J=9 and 2 Hz, 1H), 5.52 (br s, 1H), 3.96 (d, J=7 Hz, 1H), 1.42 (s, 3H), and 1.36 (s, 3H).

Provenance & Evidence