Ammonium Chloride → tert-butyl 3-hydroxy-3-(trifluoroMethyl)azetidine-1-carboxylate

Participants

Reaction Steps

To a stirred solution of tert-butyl 3-oxoazetidine-1-carboxylate (0.50 g, 2.9 mmol) and (trifluoromethyl)trimethylsilane (0.65 mL, 4.4 mmol) in tetrahydrofuran (5 mL) at 0° C. was added tetramethylammonium fluoride (0.014 g, 0.15 mmol). The reaction mixture was warmed to room temperature. After 1 h, the reaction mixture was poured into a 0.5M aqueous ammonium chloride solution (25 mL) and extracted with diethyl ether (25 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated to a crude oil. The crude oil was dissolved in tetrahydrofuran (5 mL). A 1M aqueous citric acid solution (5 mL) was added and the mixture was stirred for 1 h. The reaction mixture was partitioned between diethyl ether (25 mL) and water (10 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated to a crude oil. The residue was purified by silica gel chromatography (EtOAc/Hexanes gradient) to afford tert-butyl 3-hydroxy-3-(trifluoromethyl)azetidine-1-carboxylate as a white solid. 1H NMR (600 MHz, DMSO-D6) 4.17 (d, 2H); 3.91 (d, 2H); 1.43 (s, 9H).

Provenance & Evidence