875305-77-4

124-38-9

126811-29-8

875305-77-4

The general procedure for the synthesis of 4-chloro-1H-indole-7-carboxylic acid from carbon dioxide and 4-chloro-7-bromoindole was as follows: 560 mg (2.43 mmol) of 7-bromo-4-chloro-1H-indole was dissolved in 15 mL of tetrahydrofuran (THF). The reaction mixture was cooled to -78 °C under nitrogen protection and 4.55 mL of 1.6 M butyllithium hexane solution was slowly added, controlling the temperature to not exceed -70 °C. After the addition was completed, the reaction mixture was kept stirred at -78 °C for 30 minutes. Subsequently, the reaction mixture was warmed to 0 to 5 °C and stirring was continued. The reaction mixture was again cooled to -78°C and dry ice was added. After the reaction mixture naturally warmed to room temperature, it was stirred for 15 minutes and then poured into 100 mL of water. The aqueous phase was washed twice with ether, acidified with 1 N aqueous hydrochloric acid and then extracted twice with ether. The organic phases were combined, washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered and the solvent was concentrated under reduced pressure. The crude product was stirred with hexane for 15 min, filtered and dried to give 319 mg (67% yield) of 4-chloro-1H-indole-7-carboxylic acid as an off-white solid. Mass spectrometry (ISP) showed m/z 194.1 ([M-H]-).