反应详情

温度

-75 °C

1.56 ml (2.49 mmol) of a 1.6 M butyl lithium solution in hexane were diluted with 3.2 ml THF at −78° C. under nitrogen. 211 mg (1.24 mmol) of 5-chloro-6-fluoro-1H-indole as a 3:1 mixture of regioisomers dissolved in 0.8 ml THF were added within 15 min keeping the temperature below −70° C. After 5 min 279 mg (2.49 mmol) of potassium-tert-butylate dissolved in 1 ml THF were added within 15 min. The reaction mixture was stirred for 2 h at −75° C. to give a clear orange solution. Solid carbon dioxide was added at that temperature and the reaction mixture was allowed to warm to rt within 30 min. Water was added and the reaction mixture was extracted twice with diethyl ether. The aqueous layer was acidified with 1N aqueous HCl solution and extracted twice with diethyl ether. The combined organic layers were washed with saturated aqueous NaCl solution, dried over sodium sulfate, filtered and the solvent was evaporated. The residue was stirred with n-hexane and a trace of diethyl ether for 2 h and filtered to yield 121 mg (46 of 5-chloro-6-fluoro-1H-indole-7-carboxylic acid as a light brown solid. 1H NMR (DMSO-d6, 300 MHz): δ 13.6 (br, 1H), 11.3 (br, 1H), 8.00 (d, 1H), 7.42 (s, 1H), 6.52 (s, 1H).

1. additionwere added within 15 min
2. customthe temperature below −70° C
3. additionwere added within 15 min
4. customto give a clear orange solution
5. temperatureto warm to rt within 30 min
6. extractionthe reaction mixture was extracted twice with diethyl ether
7. extractionextracted twice with diethyl ether
8. washThe combined organic layers were washed with saturated aqueous NaCl solution
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. customthe solvent was evaporated
12. stirringThe residue was stirred with n-hexane
13. waita trace of diethyl ether for 2 h
14. filtrationfiltered