Ethyl Acetate → 4-(1-Cyanocyclopropyl)benzonitrile

Participants

Reaction Conditions

Reaction Steps

Solid KHMDS (6.82 g, 34.3 mmol) is dissolved in THF (60.0 mL) and cooled to −40° C. Cyclopropanecarbonitrile (2.30 g, 34.3 mmol) is added, and the resulting solution is stirred for 30 minutes. A solution of 4-fluorobenzonitrile (4.15 g, 34.3 mmol) in THF (20.0 mL) is added, and the mixture is stirred for 20 minutes at −40° C. followed by 2 hours at room temperature. A saturated solution of NaHCO3 (50.0 mL) is added, and the aqueous phase is extracted with EtOAc (4×40.0 mL). The combined organic phases are dried over MgSO4, filtered and concentrated on the rotovaporator. The product is purified by flash chromatography (CombiFlash), eluting with mixtures of heptanes and EtOAc (0% EtOAc to 70% EtOAc) (743 mg, 4.42 mmol, 13%). 1H NMR (400 MHz, DMSO-D6) δ ppm 1.60-1.67 (m, 2H) 1.84-1.90 (m, 2H) 7.49 (d, J=8.59 Hz, 2H) 7.85 (d, J=8.79 Hz, 2H).

Provenance & Evidence