Methyl iodide → 4-Chloro-1-methyl-1H-indole-2,3-dione

Participants

Reaction Steps

To a solution of 4-chloroisatin (CAS#6344-05-4, 3.64 g, 20.0 mmol) in acetonitrile (150 mL) was added potassium carbonate (11.1 g, 80 mmol) followed by iodomethane (2.75 mL, 44.0 mmol). The reaction was then placed at 60° C. and stirred for 40 minutes. The reaction was then cooled to room temperature, filtered and concentrated to 10% of the original volume. The reaction was then diluted with dichloromethane, water, and brine. The layers were separated and the aqueous layer was extracted two additional times with dichloromethane. The organic extracts were combined, dried over anhydrous sodium sulfate filtered, and concentrated to provide 4-chloro-1-methyl-1H-indole-2,3-dione as an orange solid without the need for further purification. The 4-chloro-1-methyl-1H-indole-2,3-dione (1.55 g, 7.92 mmol) was then treated with hydrazine hydrate (14.8 ml, 475 mmol). The reaction was then placed at 70° C. and heated to 130° C. over 20 minutes. The reaction was stirred at 130° C. for 45 minutes, at which time the reaction was placed at room temperature and cooled by the addition of ice. Once the reaction was cooled to room temperature it was diluted with dichloromethane and water and the layers were then separated. The aqueous layer was extracted an additional two times with dichloromethane, and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (ethanol-dichloromethane 0 to 2%) to afford 4-chloro-1-methyl-1,3-dihydro-indol-2-one; MS: (ES+) m/z 182.0 (M+H)+.

Provenance & Evidence