反应详情

温度

70 °C

Iron (Alrich cat#20930-9, 24.9 g, 445 mmol) and ammonium chloride (4.80 g, 89.7 mmol) were added to a suspension of ethyl 5-cyano-4-(3-fluoro-4-nitrophenyl)-1H-pyrrole-3-carboxylate (45.0 g, 148 mmol) in ethanol (540 mL) and water (180 mL) equipped with an overhead stirrer. The reaction was warmed (70° C.) for 2 h, and then cooled to rt. The mixture was diluted with methanol (500 mL) and then filtered through a well-packed pad of Celite®. The filter cake was thoroughly rinsed with methanol (1 L) and acetonitrile (2 L) and the combined filtrate was evaporated. The residue was dissolved in ethyl acetate (1.5 L) then washed with water (500 mL) and brine (500 mL). The organic layer was dried over sodium sulfate and evaporated under reduced pressure to afford the desired product (38.0 g, 94%) containing trace impurities (<5%). The material was used in the next step without further purification. 1H NMR (300 MHz, DMSO-d6) δ 13.36 (s, 1H), 8.25 (dd, J=12.8, 2.0 Hz, 1H), 6.92-6.97 (m, 1H), 6.72-6.79 (m, 1H), 5.35 (s, 2H), 4.10 (q, J=7.0 Hz, 2H), 1.16 (t, J=7.0 Hz, 3H); ES-MS m/z 274.3 (MH)+; HPLC RT (Method A) 2.62 min.

1. customequipped with an overhead stirrer
2. temperaturecooled to rt
3. filtrationfiltered through a well-packed pad of Celite®
4. washThe filter cake was thoroughly rinsed with methanol (1 L) and acetonitrile (2 L)
5. customthe combined filtrate was evaporated
6. dissolutionThe residue was dissolved in ethyl acetate (1.5 L)
7. washthen washed with water (500 mL) and brine (500 mL)
8. dry with materialThe organic layer was dried over sodium sulfate
9. customevaporated under reduced pressure