Sodium Cyanide → Methyl 5-cyano-2-(4-fluorophenoxy)nicotinate

Participants

Reaction Steps

A mixture of methyl 5-bromo-2-(4-fluorophenoxy)nicotinate (step 1, 163 mg, 0.50 mmol), sodium cyanide (49 mg, 1.0 mmol), tetrakis(triphenylphohphine) palladium(0) (29 mg, 0.025 mmol), and copper iodide (9.5 mg, 0.05 mmol) in propionitrile (4.0 mL) was heated under reflux for 4.5 h with stirring. The reaction mixture was filtered through a pad of Celite®. The filtrate was partitioned between water (10 mL) and dichloromethane (30 mL). The organic phase was separated, dried (sodium sulfate), and concentrated. The residue was purified by TLC plate developing with hexane/ethyl acetate (3/1) to afford 97 mg (71%) of the title compound: 1H-NMR (CDCl3) δ 8.5 (2H, m), 7.14 (2H, d, J=1.2 Hz), 7.12 (2H, s), 3.99 (3H, s); MS (ESI) m/z 272 (M+).

Provenance & Evidence