Sodium Hydroxide → 4,4,4-Trifluoro-3-(phenylamino)butanoic acid

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Reaction Steps

A solution of compound 326 (2.16 g, 6.48 mmol) and sodium hydroxide (2.60 g, 64.8 mmol) in water (5.2 mL) and ethanol (26 mL) was stirred at room temperature for 24 h. The solvents were removed under reduced pressure leaving a white solid which was triturated in ether, isolated by filtration, rinsed with ether and dried under high vacuum. The white solid was dissolved in water (12 mL), and the solution was neutralized to pH 4 with a 3N HCl solution, extracted twice with EtOAc, the combined organic layers were dried over sodium sulfate and the solvent removed under reduced pressure. The solid was dissolved in dry toluene (20 mL), heated to reflux for 1 h with continuous stirring, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent EtOAc-hexane, gradient 0:100 to 40:60) to afford title compound 327 (204 mg, 0.87 mmol, 13% yield) as a beige solid. 1H NMR (400 MHz, CDCl3) δ ppm: 7.24-7.18 (m, 2H), 6.82 (tt, J=7.2, 1.0 Hz, 1H), 6.75-6.71 (m, 2H), 4.55-4.45 (m, 1H), 2.89 (dd, J=16.0, 4.4 Hz, 1H), 2.67 (dd, J=16.0, 8.8 Hz, 1H). LRMS (M−1) 231.9 (100%).

Provenance & Evidence