反应详情

温度

0 °C

A mixture of 5-bromo-6-chloro-1H-indole (15.1 g, 65.5 mmol), tetrahydrofuran (100 mL), pyridine (18.4 mL, 229 mmol) and DMAP (808 mg, 6.55 mmol) was cooled to 0° C. and treated with trichloroacetyl chloride (22.1 mL, 197 mmol) dropwise over 30 minutes. The reaction mixture was stirred at room temperature for 64 hours then cooled to 10° C. Methanol (100 mL) was added dropwise to the reaction mixture over 10 minutes, producing a dark homogenous solution. Potassium carbonate (54.9 g, 393 mmol) was then added portion-wise and the ice bath was removed. Stirring was kept at a vigorous pace and allowed to continue for 2 hours, during which time the reaction turned dark green and produced an exotherm. The reaction was quenched slowly with 1M HCl (until acidic pH was maintained) and diluted with ethyl acetate. The organic layer was washed with 1M HCl. The aqueous layer was back-extracted twice with ethyl acetate. The combined organic layers were then washed carefully with saturated sodium bicarbonate solution followed by brine. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo to provide the title compound as a brown solid (18.7 g, 99%).

1. temperaturethen cooled to 10° C
2. customproducing a dark homogenous solution
3. customthe ice bath was removed
4. stirringStirring
5. waitto continue for 2 hours, during which time
6. customproduced an exotherm
7. customThe reaction was quenched slowly with 1M HCl (until acidic pH was maintained)
8. additiondiluted with ethyl acetate
9. washThe organic layer was washed with 1M HCl
10. extractionThe aqueous layer was back-extracted twice with ethyl acetate
11. washThe combined organic layers were then washed carefully with saturated sodium bicarbonate solution
12. dry with materialThe organic layer was dried over magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated in vacuo