Sodium hydride → 5,7-difluoro-1H-indole

Participants

Reaction Steps

Fresh sodium ethoxide is prepared by carefully adding NaH (16 g of 60% oil dispersion, 400 mmol) to 550 mL of ethanol under N2. 2-(Trimethylsilylethynyl)-4,6-difluoro-N-carbethoxyaniline (28 g, 100 mmol) in 150 mL of ethanol is added and reaction is stirred at room temperature approximately 45 minutes, while monitoring by TLC (20% ethyl acetate/hexane, UV) until all the starting material is consumed. The mixture is heated to reflux and monitored by TLC until the intermediate material is consumed (approx. 1 hour). Reaction is cooled to room temperature, concentrated, diethylether is added, washed with H2O, brine, dried (Na2SO4), filtered, concentrated, and is purified by flash chromatography (SiO2, ethyl acetate/hexane gradient) to yield 12 g of 5,7-difluoro-indole (78%).

Provenance & Evidence