反应详情

温度

80 °C

Sodium hydride (60% dispersion in mineral oil, 3.02 g, 75.6 mmol) was added to a solution ethyl 5-cyano-4-(nitrophenyl)-1H-pyrrole-3-carboxylate (17.97 g, 63.00 mmol) in DMF (625 mL). The solution was stirred at it for 15 min and then (aminooxy)(diphenyl)phosphine oxide (17.63 g, 75.59 mmol) was added, and the solution was heated (80° C.) for 17 h. Upon cooling to it aqueous saturated sodium bircarbonate solution (500 mL) was added followed by ethyl acetate (400 mL). The layers were separated and the aqueous layer was back extracted with ethyl acetate (2×200 mL). The combined organic layers dried over sodium sulfate and concentrated to dryness. The crude material was triturated with dichloromethane-hexanes (1:1 v/v 400 mL). The solid was collected, washed with hexanes (100 mL), and dried under vacuum. The material was suspended in ethyl acetate (500 mL) and, heated to reflux for 15 min, and then filtered. The filtrate was concentrated in vacuo to afford the desired product (14.15 g, 75%). 1H-NMR (300 MHz, DMSO-d6) 8.25-8.31 (m, 2H), 7.73 (s, 1H), 7.67-7.73 (m, 2H), 6.71 (br s, 2H), 4.12 (q, J=7.1 Hz, 2H), 1.16 (t, J=7.1 Hz, 3H); HPLC RT (Method A) 2.91 min; TLC Rf=0.30 (95:5 v/v CH2Cl2-EtOAc).

1. additionwas added
2. customThe layers were separated
3. extractionthe aqueous layer was back extracted with ethyl acetate (2×200 mL)
4. dry with materialThe combined organic layers dried over sodium sulfate
5. concentrationconcentrated to dryness
6. customThe crude material was triturated with dichloromethane-hexanes (1:1 v/v 400 mL)
7. customThe solid was collected
8. washwashed with hexanes (100 mL)
9. customdried under vacuum
10. temperatureheated
11. temperatureto reflux for 15 min
12. filtrationfiltered
13. concentrationThe filtrate was concentrated in vacuo