Carbon Dioxide → 5,6-difluoro-1H-indole-7-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

1.25 ml (2 mmol) of a 1.6 M butyl lithium solution in hexane were diluted with 4 ml THF at −78° C. under nitrogen. 224 mg (2 mmol) of potassium-tert-butylate and then 156 mg (1 mmol) of 5,6-difluoro-1H-indol were added. The reaction was exothermal and an orange solution was obtained, which was stirred for 2 h at −75° C. 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 three times with diethyl ether. The aqueous layer was acidified with 1N aqueous HCl solution and extracted three times 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 15 min and filtered to yield 100 mg (51%) product as a yellow solid. 1H NMR (DMSO-d6, 300 MHz): 13.6 (br, 1H), 11.2 (br, 1H), 7.85 (dd, 1H), 7.42 (s, 1H), 6.53 (s, 1H).

Provenance & Evidence