反应详情

To a stirred solution of sodium nitrite (68.4 g, 991.3 mmol) in water (1425 mL) was added methyl 6-bromo-1H-indole-4-carboxylate (20.64 g, 81.25 mmol) at RT and the mixture stirred for 15 min at RT. To the mixture was added 6N HCl (159.6 mL) slowly dropwise over a period of 1 h and the reaction mixture was then stirred at room temperature for 48 h. The reaction mixture was extracted with 10% THF in ethyl acetate (5×500 mL). The combined organic layers were washed with water, brine, dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated to ⅓ volume and cooled in freezer for 4 h. Precipitated solids were filtered and washed with cold ethyl acetate and dried under high vacuum to afford the title compound as an off white solid (13.7 g, 59.6%). 1H NMR (DMSO-d6, 400 MHz): δ 3.905 (s, 3H), 7.754 (s, 1H), 8.183 (s, 1H), 10.274 (s, 1H), 14.563 (brs, 1H). LCMS (ES+): 281.06 [M−H] ion present.

1. stirringthe reaction mixture was then stirred at room temperature for 48 h
2. extractionThe reaction mixture was extracted with 10% THF in ethyl acetate (5×500 mL)
3. washThe combined organic layers were washed with water, brine
4. dry with materialdried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationThe filtrate was concentrated
7. temperaturecooled in freezer for 4 h
8. customPrecipitated solids
9. filtrationwere filtered
10. washwashed with cold ethyl acetate
11. customdried under high vacuum