Dimethylacetamide → 4-Cyclohexyl-3-(trifluoromethyl)benzonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-bromo-3-(trifluoromethyl)benzonitrile (6 g, 24.00 mmol), DMA (30 mL), cuprous iodide (0.914 g, 4.80 mmol) and 1,1′-bis(diphenylphosphino) ferrocenedichloro palladium(II) dichloromethane complex (1.756 g, 2.400 mmol) was bubbled with nitrogen for 5 min. before 0.5 M THF solution of cyclohexylzinc bromide (100 mL, 50.0 mmol) was added over 20 min. via cannula at room temperature. The black reaction mixture was stirred at 60° C. overnight. The reaction mixture was concentrated under reduced pressure. EtOAc (50 mL), water (100 mL) and saturated aqueous ammonium chloride solution (30 mL) were added. The solid was filtered off over a celite pad and washed with ethyl acetate (3×20 mL). The aqueous layer was separated and extracted with ethyl acetate (50 mL). The combined organic solutions were washed with 1 N aqueous HCl (2×40 mL) and then brine (40 mL), dried (sodium sulfate) and concentrated under reduced pressure. Flash chromatography purification (silica gel column, 20→100% ethyl acetate in hexanes) afforded 4-cyclohexyl-3-(trifluoromethyl)benzonitrile (2.77 g, 10.94 mmol, 45.6% yield) as a solid. The compound had an HPLC retention time=3.44 min. (condition C); LC/MS [M+H2O]+1=272.2.

Provenance & Evidence