4-Bromobutyronitrile → HCID 23003165, compound

Participants

Reaction Steps

To a solution of 5-(2,6-dichlorobenzyloxy)-1H-indole (2.0 g, 6.85 mmol) in dimethylformamide (30 mL) at ambient temperature was added sodium hydride (0.41 g, 10.3 mmol, 60% in mineral oil). After stirring at ambient temperature for 1 h, 4-bromobutyronitrile (1.01 g, 0.68 mL, 6.85 mmol) was added followed by the addition of tetrabutylammonium iodide (0.25 g, 0.68 mmol). After stirring at room temperature for 24 h, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine and dried (Na2SO4). Purification by flash column chromatography (silica gel, hexanes/ethyl acetate) yielded a mixture (1.37 g total weight) of desired product (85%) and undesired product 3-[5-(2,6-dichlorobenzyloxy)indole-1-yl]butyronitrile (15%). The two component mixture (0.12 g total weight) was treated with sodium methoxide (catalytic) in methanol/THF at room temperature for 16 h. The undesired product was decomposed and purification by flash column chromatography (silica gel, hexanes/ethyl acetate) afforded the desired product as a clear oil (0.1 g). MS(ES) m/e 359.0 [M+H]+.

Provenance & Evidence