Acetone Cyanohydrin → (E)-4-(1-(4-fluorophenyl)cyclohexyl)but-3-enenitrile

Participants

Reaction Steps

To a solution of (E)-3-(1-(4-fluorophenyl)cyclohexyl)prop-2-en-1-ol (Intermediate I-11A, 912 mg, 3.89 mmol) and triphenylphosphine (1531 mg, 5.84 mmol) in THF (20 mL) at −20° C. was added diethyl azodicarboxylate (0.924 mL, 5.84 mmol) dropwise and the mixture was stirred at a temperature in the range of from about 20 to about −10° C. for 20 mins. Then 2-hydroxy-2-methylpropanenitrile (0.109 mL, 1.196 mmol) was added slowly at −20° C., and the mixture was stirred for 1 hr at a temperature in the range of from about −20 to about 10° C. and for 20 hrs at room temperature. The reaction was quenched with a few drops of methanol and stirred for 20 mins. After evaporation of the solvent the residue was purified by column chromatography (80 g silica gel) eluting with 1:9 followed by 2:8 ethyl acetate-hexane to give the desired (E)-4-(1-(4-fluorophenyl)cyclohexyl)but-3-enenitrile (760 mg, 80% yield) as an oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.25-7.30 (2H, m), 7.01 (2H, t, J=8.80 Hz), 5.85 (1H, d, J=15.63 Hz), 5.10 (1H, ddd, J=15.74, 5.72, 5.61 Hz), 3.06 (2H, dd, J=5.61, 1.65 Hz), 1.98-2.06 (2H, m), 1.77-1.86 (2H, m), 1.41-1.60 (6H, m).

Provenance & Evidence