反应详情

温度

-78 °C

492 mg (2.30 mmol) of 7-bromo-4-fluoro-1H-indole were dissolved in 14 ml THF. The reaction mixture was cooled to −78° C. and 4.31 ml of a 1.6 M butyl lithium solution in hexane were added under nitrogen in such a way, that the temperature did not exceed a maximum of −70° C. The yellow solution was stirred at 0 to 5° C. after complete addition for 30 min. The reaction mixture was cooled to −78° C. and dry ice was added. The reaction mixture was warmed to rt, stirred for 15 min and poured onto 100 ml water. The aqueous layer was washed twice with diethyl ether, acidified with 1N aqueous HCl solution and extracted twice with DCM. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and the solvent was evaporated. The crude residue was stirred with hexane for 15 min, filtered and dried to yield 328 mg (80%) of 4-fluoro-1H-indole-7-carboxylic acid as an off-white solid. MS (ISP) 177.9 (M−H)−.

1. customa maximum of −70° C
2. additionafter complete addition for 30 min
3. temperatureThe reaction mixture was cooled to −78° C.
4. temperatureThe reaction mixture was warmed to rt
5. stirringstirred for 15 min
6. washThe aqueous layer was washed twice with diethyl ether
7. extractionextracted twice with DCM
8. washThe combined organic layers were washed with saturated aqueous sodium chloride solution
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. customthe solvent was evaporated
12. stirringThe crude residue was stirred with hexane for 15 min
13. filtrationfiltered
14. customdried