反应详情

温度

60 °C

Sodium hydride (60% dispersion in oil, 1.7 g, 43 mmol) was added in portions to a solution of ethyl 4-(4-amino-3-fluorophenyl)-5-cyano-1H-pyrrole-3-carboxylate (9.0 g, 33 mmol) in DMF (290 mL). The suspension was stirred for 30 min and then (aminooxy)(diphenyl)phosphine oxide (9.9 g, 43 mmol) was added. The reaction was warmed (60° C.) for 4 h and then cooled to rt. The reaction was quenched by slow addition of water (10 mL) and the solvents were evaporated under reduced pressure. The residue was dissolved in ethyl acetate (500 mL) and the solution was washed with saturated aqueous sodium bicarbonate solution (2×250 mL) and brine (250 mL). The organic layer was dried over sodium sulfate and evaporated. The residue was triturated with diethyl ether to give the desired product (7.8 g, 82%); 1H NMR (300 MHz, DMSO-d6) δ 7.57 (s, 1H), 7.05 (dd, J=12.7, 2.0 Hz, 1H), 6.91-6.95 (m, 1H), 6.75 (dd, J=9.5, 8.4 Hz, 1H), 6.57 (s, 2H), 5.36 (s, 2H), 4.09 (q, J=7.0 Hz, 2H), 1.16 (t, J=7.0 Hz, 3H); ES-MS m/z 289.0 (MH)+; HPLC RT (Method B) 2.61 min.

1. temperaturecooled to rt
2. customThe reaction was quenched by slow addition of water (10 mL)
3. customthe solvents were evaporated under reduced pressure
4. dissolutionThe residue was dissolved in ethyl acetate (500 mL)
5. washthe solution was washed with saturated aqueous sodium bicarbonate solution (2×250 mL) and brine (250 mL)
6. dry with materialThe organic layer was dried over sodium sulfate
7. customevaporated
8. customThe residue was triturated with diethyl ether