Imidazole → 2-Cyanomethyl-1,2,3,4-tetrahydroquinoline

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-hydroxymethyltetrahydroquinoline (35.9 g, 0.22 mol), imidazole (35.95 g, 0.528 mol), and triphenylphosphine (69.24 g, 0.264 mol) in a mixed solvent of 5:1 toluene/acetonitrile (750 mL) was added iodine (61.42 g, 0.242 mol) at 0° C. The mixture was stirred for 15 min at 0° C. and for 30 min at room temperature. Aqueous sodium thiosulfate solution (200 mL) was added. The organic layer was separated, washed with brine, dried over magnesium sulfate, and concentrated. The residue was triturated with diethyl ether and the insoluble materials were removed by filtration. The filtrate was concentrated and the residual oil was dissolved in DMF (200 mL). To the solution was added sodium cyanide (43.2 g, 0.881 mol) and the mixture was heated at 80° C. for 10 h. The resulting mixture was poured into ice-water and extracted with a mixture of toluene and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography with 1:1 hexane/dichloromethane to 100% dichloromethane as eluents to give 31.6 g of the title compound (94%).

Provenance & Evidence