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

Participants

Reaction Conditions

Reaction Steps

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

Provenance & Evidence