反应详情

温度

70 °C

Ethyl 5-(benzyloxy)-1H-indole-2-carboxylate (25 g, 85 mmol) was dissolved in toluene (125 mL) and 60% sodium hydride in mineral oil (7.79 g, 195 mmol) was added portionwise. The reaction was stirred for 50 min and butyl acrylate (26.6 mL, 186 mmol) was added. The reaction was stirred at room temperature for 1.5 h and additional butyl acrylate (20 mL) was added. After stirring for 30 min, the solution was warmed to 70° C. and stirred for 1 h. The reaction was cooled to room temperature and sodium hydride (4.0 g) was added. The reaction was warmed to 70° C. causing the reaction to reflux. The heat source was removed and butyl acrylate (15 mL) was added and heating at 70° C. was resumed. After 30 min, the heat source was removed and the reaction was left to stir for 16 h. Water (25 mL) was added followed by 1.0 M HCL (250 mL) and 12 M HCL (50 mL). The aqueous layer was removed and the toluene was washed two times with water (100 mL). The toluene layer was concentrated under reduced pressure and the concentrate was taken up in acetic acid (120 mL) and water (12 mL). The reaction mixture was heated under reflux and stirred for 24 h. The reaction mixture was cooled to room temperature and water (200 mL) was added. The aqueous mixture was diluted with ethyl acetate and washed with water and brine. The ethyl acetate layer was filtered through a pad of Celite® and the filtrate was concentrated under reduced pressure. The residue was purified by crystallization from methanol to provide the title compound (8.0 g). LCMS m/z=278.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 3.20 (t, J=6.6 Hz, 2H), 4.41 (t, J=6.2 Hz, 2H), 5.11 (s, 2H), 6.91 (s, 1H), 7.13 (dd, J=9.0, 2.4 Hz, 1H), 7.19 (d, J=2.4 Hz, 1H), 7.30-7.42 (m, 4H), 7.44-7.49 (m, 2H).

1. stirringThe reaction was stirred at room temperature for 1.5 h
2. stirringAfter stirring for 30 min
3. stirringstirred for 1 h
4. temperatureThe reaction was cooled to room temperature
5. temperatureThe reaction was warmed to 70° C.
6. customthe reaction
7. temperatureto reflux
8. customThe heat source was removed
9. additionbutyl acrylate (15 mL) was added
10. temperatureheating at 70° C.
11. waitAfter 30 min
12. customthe heat source was removed
13. waitthe reaction was left
14. stirringto stir for 16 h
15. additionWater (25 mL) was added
16. customThe aqueous layer was removed
17. washthe toluene was washed two times with water (100 mL)
18. concentrationThe toluene layer was concentrated under reduced pressure
19. temperatureThe reaction mixture was heated
20. temperatureunder reflux
21. stirringstirred for 24 h
22. temperatureThe reaction mixture was cooled to room temperature
23. additionwater (200 mL) was added
24. additionThe aqueous mixture was diluted with ethyl acetate
25. washwashed with water and brine
26. filtrationThe ethyl acetate layer was filtered through a pad of Celite®
27. concentrationthe filtrate was concentrated under reduced pressure
28. customThe residue was purified by crystallization from methanol