5.0 g (33.0 mmol) of commercially available 5-chloro-1H-indole was dissolved in 50 mL of anhydrous N,N-dimethylformamide (DMF) and the reaction system was kept at 0°C. Slowly 7.35 g (35.0 mmol) of trifluoroacetic anhydride was added dropwise to the above solution. After the dropwise addition, the reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction, the mixture was slowly poured into 200 mL of ice water and the precipitate was collected by filtration. The resulting precipitate was suspended in 200 mL of 20% sodium hydroxide (NaOH) aqueous solution and heated at reflux overnight. After cooling, the aqueous phase was extracted twice with dichloromethane (100 mL each time). The organic phases were combined and the aqueous phase was acidified to pH 2-3 with concentrated hydrochloric acid to precipitate a solid. The crystalline product was collected by filtration and washed with a small amount of cold water. Finally, the product was dried in a vacuum drying oven to give 6.0 g of 5-chloroindole-3-carboxylic acid in 93% yield.
