反应详情

To a cooled (0° C.) solution of methyl 6-bromo-1H-indole-4-carboxylate (1.0 g, 3.94 mmol) solid in N,N-dimethylformamide (25 mL) was added sodium hydride (0.173 g, 4.33 mmol). The reaction was stirred for 15 min, at which time 2-bromopropane (0.554 mL, 5.90 mmol) was added. The reaction was then allowed to warm to RT and was maintained overnight. LCMS showed about 25% starting material remaining. The reaction was heated at 45° C. for 4 h, but no further conversion was noted. The reaction vessel was put back into an ice bath and stirred for 15 min. Then excess NaH (60%) was added, stirred for 10 min, and then 2-bromopropane (excess) was added. The ice bath was removed and the reaction stirred for 1 h. Approximately half of the reaction volume was removed in vacuo and poured into saturated NH4Cl (200 mL). This was extracted with ether (2×) and the combined organics were washed with brine, dried (MgSO4), and concentrated. Purification by column chromatography (80 g Isco silica column; Gradient B: 5-25%, A: hexane, B: ethyl acetate) gave methyl 6-bromo-1-(1-methylethyl)-1H-indole-4-carboxylate (0.53 g, 1.718 mmol, 43.7% yield).

1. additionwas added
2. temperaturewas maintained overnight
3. temperatureThe reaction was heated at 45° C. for 4 h
4. customThe reaction vessel was put back into an ice bath
5. stirringstirred for 10 min
6. customThe ice bath was removed
7. stirringthe reaction stirred for 1 h
8. customApproximately half of the reaction volume was removed in vacuo
9. additionpoured into saturated NH4Cl (200 mL)
10. extractionThis was extracted with ether (2×)
11. washthe combined organics were washed with brine
12. dry with materialdried (MgSO4)
13. concentrationconcentrated
14. customPurification by column chromatography (80 g Isco silica column