1,3-Dibromopropane → 1-(4-Bromo-2-fluorophenyl)cyclobutanecarbonitrile

Participants

Reaction Steps

A solution of (4-bromo-2-fluoro-phenyl)-acetonitrile (4.0 g, 18.7 mmol) from step 1 and 1,3-dibromopropane (2.1 mL, 20.6 mmol) in Et2O (5 mL) was slowly added to a slurry of NaH (1.64 g, 41.1 mmol, 60% in mineral oil) in DMSO (19 mL) at room temperature, being careful to keep the temperature below 35 degrees Celsius. The reaction was stirred for 2.5 hours, and then poured into 150 mL of saturated ammonium chloride. To this mixture was added CH22Cl2, and the layers were separated. The aqueous layer was extracted with 2×50 mL of CH2Cl2, and the organic layers were combined. After drying the liquid over MgSO4, the solids were filtered away, and the organic was concentrated to an oil. It was further purified by flash chromatography (90 g SiO2, 1:99->1:20 (EtOAc/Hexanes) to give the desired product (2.81 g, 59%). 1H NMR (400 MHz, CDCl3) δ: 2.06-2.16 (m, H), 2.51-2.63 (m, H), 2.66-2.76 (qd, J=9347 Hz, 2H), 2.86-2.94 (m, 2H), 7.16-7.22 (t, J=8.21 Hz, H), 7.30-7.41 (m, 2H).

Provenance & Evidence