Toluene → 2-Fluoro-4-methylbenzonitrile

Participants

Reaction Conditions

Reaction Steps

To a deoxygenated solution of 4-bromo-3-fluorotoluene (25.0 g, 132 mmol) in DMF (500 mL) was added Zn(CN)2 (10.1 g, 86 mmol) and Pd(PPh3)4 (15 g, 13 mmol). The reaction was stirred at 100° C. for 18 hrs, then cooled to room temperature. The solution was poured into toluene (1 L), washed with 30% aq. NH4OH (2×1 L), then brine (800 mL), then dried (Na2SO4), filtered, and concentrated in vacuo to provide the crude product. Purification by silica gel chromatography, eluting with a gradient of hexane—0% to 7% EtOAc, yielded the titled product.

Provenance & Evidence