Water → 5-Chloromethyl-1-(4-fluorophenyl)-1h-indole

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(4-fluorophenyl)-5-hydoxymethyl-1H-indole (10a) (21.5 g) and triethyl amine (21.5 mL) in dichloromethane a solution of methanesulfonyl chloride (15.3 g) in dichloromethane was added at 0-5° C. After stirring at 0-5° C. for 2 h, water (600 mL) was added the phases were separated and the aqueous phase was extracted with dichloromethane (500 mL). The combined organic phases were dried (MgSO4) and the solvents evaporated affording 5-chloromethyl-1-(4-fluorophenyl)-1H-indole as an oil (27.5 g). A solution of the crude chloromethyl derivative in dimethyl sulfoxide was added to a solution of sodium cyanide in dimethyl sulfoxide at 80° C. After heating of the reaction mixture at 80° C. for further 40 minutes, the reaction mixture was cooled to room temperature and water (900 ml) was added. The resulting mixture was extracted with diethyl ether (2×1.5 L) and the combined organic phases were washed with brine (2×1.5 L). Drying of the combined organic phases (Na2SO4), evaporation of the solvents and purification by column chromatography on silica gel (ethyl acetate/heptane 1:3) afforded pure 5-cyanomethyl-1-(4-fluorophenyl)-1H-indole as an oil (8.2 g): 1H NMR (CDCl3) δ 3.80 (s, 2H), 6.60 (d, 1H), 7.05-7.25 (m, 3H), 7.25 (d, 1H), 7.35-7.45 (m, 3H), 7.60 (broad s, 1H).

Provenance & Evidence