Benzene, 1-fluoro-4-(trifluoromethyl)- → 1-(4-(Trifluoromethyl)phenyl)cyclopentanecarbonitrile

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 4-fluorobenzotrifluoride (5.0 g, 30.47 mmol) in toluene (40 mL) was added cyclopentanecarbonitrile (10.5 mL, 100.55 mmol) followed by a solution of 0.5 M KHMDS in toluene (92 mL, 45.71 mmol). The reaction mixture was heated to 70° C. and stirred for 14 hours. After cooling to RT, the reaction mixture was quenched with 1 M HCl until pH<7. The layers were separated and the organic layer was washed with saturated NaHCO3, water, brine, dried over MgSO4, filtered, and concentrated in vacuo. Purification via silica gel chromatography (6:1 hexanes:EtOAc) afforded 7.53 g of a mixture of compound A and residual cyclopentanecarbonitrile. Because these two compounds were not easily separable by chromatography, this mixture was carried directly to the next step.

Provenance & Evidence