Chloromethyl ethyl ether → 1-ethoxymethyl-5-methoxy-3-(1-methylethoxy)-1H-indole-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

5-Methoxy-3-(1-methylethoxy)-1H-indole-2-carboxamide (328 mg, 1.32 mmol) in 5 mL of dimethylformamide is added to a suspension of sodium hydride (60% by weight) (67 mg, 1.67 mol) in 5 mL of dimethylformamide. After 1.5 hours the mixture is cooled to 0° C. and chloromethyl ethyl ether (160 μL, 1.72 mmol) is added dropwise, and the solution is stirred at 0° C. for 20 minutes and then at room temperature for 1.5 hours. The reaction mixture is diluted with 1:1 hexane:ethyl acetate and washed with brine. The organic layer is dried over MgSO4, filtered, and concentrated in vacuo. Chromatography eluting with 1:1 ethyl acetate:hexane gives 240 mg (51%) of 1-ethoxymethyl-5-methoxy-3-(1-methylethoxy)-1H-indole-2-carboxamide; mp 110°-112° C.

Provenance & Evidence