Carbon Dioxide → 5-chloro-6-fluoro-1H-indole-7-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

35 ml THF was cooled down to −75° C. under argon and 19.05 ml of a 1.6M solution of n-BuLi in hexane (30.5 mmol) were added. Then a solution of 2.35 g of 5-chloro-6-fluoro-1H-indole (13.7 mmol) in 9 ml THF was added dropwise (temperature kept between −70 and −75° C.) over 15 min. After 5 additional min stirring at this temperature a solution of 3.7 g potassium tert-butylate in 15 ml THF was added over 10 min (temperature kept between −70 and −75° C.). The brown solution was stirred 2 h at the same temperature and then treated with a large excess of solid CO2. The temperature was then raised to 10° C. over a period of 75 min, and treated with 30 ml water. After separation of the organic phase, the aqueous phase was extracted with 2×20 ml diethylether, treated with concentrated HCl until pH 1. The suspension was then filtered, the solid washed with water and dried in high vacuo. The residue was stirred with 10 ml hexane/diethylether 9:1 for 15 min and filtered, washed with 5 ml of the same mixture and the collected solid dried in high vacuo, leading to 2.2 g of 5-chloro-6-fluoro-1H-indole-7-carboxylic acid as a light brown solid (75%). MS: 212.2 (M−H)−.

Provenance & Evidence