Trifluoroacetic acid → HCID 131735434, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of trifluoroacetic acid (20.0 mL) and tetrahydrofuran (10.0 mL) was added sodium triacetoxyborohydride (10.59 g, 49.97 mmol, 10.0 equiv.) in portions with stirring under nitrogen. This mixture was stirred for 10 min at room temperature and then cooled to −5° C. A solution of 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (1.71 g, 5.0 mmol) and tert-butyl(2-oxoethyl)carbamate (Sigma-Aldrich) (1.99 g, 12.5 mmol, 2.5 equiv.) in THF (15.0 mL) was added drop-wise over 30 min with stirring while maintaining the temperature below 0° C. The reaction was stirred at −5 to 0° C. and additional portions of tert-butyl(2-oxoethyl)carbamate (0.20 g, 1.2 mmol, 0.24 equiv.) in THF (1.0 mL) were added drop-wise at 20 min, 40 min at 4 h intervals. HPLC indicated reaction completed after 5.25 h. The reaction mixture was poured into the ice-cold sodium bicarbonate (500 mL) and this solution was stirred at room temperature overnight. The precipitate was collected by filtration and washed with brine. The resulting residue was mixed with heptane (40 mL) and diethyl ether (40 mL) and stirred at room temperature for 5 h. The precipitate was collected by filtration, washed with diethyl ether and dried in a vacuum oven to give the desired product (1953 mg, 80.5%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.08 (m, 1H), 7.71 (m, 1H), 7.59 (t, 1H, J=8.7 Hz), 6.94 (m, 1H), 6.52 (m, 1H), 3.32 (m, 2H), 3.15 (m, 2H), 1.36 (s, 9H); C17H18BrFN6O5 (MW 485.26); LCMS (EI) m/e 507/509 (M++Na).

Provenance & Evidence