反应详情

温度

0 °C

Sodium hydride (60% suspension in mineral oil, 5.98 g) was added in portions to a stirred, cooled (0° C.) solution of 5-chloro-2-(4-chlorophenyl)-1H-indole-3-propanoic acid (Description 30, 10 g, 30 mmol) in dimethylformamide (100 mL) and the mixture was stirred at 0° C. for 30 min. Iodomethane (9 mL) was added in one portion and the mixture was stirred at room temperature for 30 min. Water (1.5 L) was added and the mixture was extracted with ether (3×400 mL). The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was dissolved in methanol (240 mL) and aqueous sodium hydroxide (4M, 60 mL) was added. The mixture was heated under reflux for 1 h., cooled and the pH was adjusted to 1.0 with hydrochloric acid (2M). The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was triturated with hexane and the solid was collected and dried in vacuo to give the title compound (7.5 g, 72%). 1H NMR (360 MHz, CDCl3) δ 7.58 (1H, d, J 1.8 Hz), 7.44-7.48 (2H, m), 7.18-7.30 (4H, m), 3.53 (3H, s), 2.96-3.00 (2H, m), and 2.54-2.59 (2H, m).

1. stirringthe mixture was stirred at room temperature for 30 min
2. extractionthe mixture was extracted with ether (3×400 mL)
3. dry with materialThe combined organic fractions were dried (MgSO4)
4. customthe solvent was evaporated under reduced pressure
5. dissolutionThe residue was dissolved in methanol (240 mL)
6. additionaqueous sodium hydroxide (4M, 60 mL) was added
7. temperatureThe mixture was heated
8. temperatureunder reflux for 1 h.
9. temperaturecooled
10. customThe layers were separated
11. extractionthe aqueous layer was extracted with ethyl acetate
12. dry with materialThe combined organic fractions were dried (MgSO4)
13. customthe solvent was evaporated under reduced pressure
14. customThe residue was triturated with hexane
15. customthe solid was collected
16. customdried in vacuo