Carbon Dioxide → 5-iodo-1-methyl-1H-indole

Participants

Reaction Steps

To a solution of 5-iodoindole (75 g, 0.31 mol) in dry THF (750 mL), at −78° C. was added sodium hydride (60% in mineral oil, 14.85 g, 0.37 mol) in one portion. The suspension was stirred at −78° C. for 1 hour after which iodomethane (28.8 mL, 0.46 mol) was added. The reaction mixture was stirred overnight with a slow elevation of temperature to room temperature (no more dry ice was added). Ether (600 mL) and hexane (1.2 L) were added and the mixture was washed with brine (1.6 L) and water (1.5 L), dried over Na2SO4 and filtered. The solution was concentrated and the residual brown solid was recrystallized from hexane to give the title compound (66 g). The impure fraction from the mother liquor was flash chromatographed (8% EtOAc in hexane) to give an additional quantity of desired product (12.5 g, combined yield of 99%). MS (DCI/NH3) m/e 258 (M+H)+.

Provenance & Evidence