Phosphorus oxychloride → 6-Chloro-4-(trifluoromethyl)nicotinonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-chloro-4-(trifluoromethyl)nicotinamide (0.847 g, 3.77 mmol, Preparation #27) and POCl3 (7.03 mL, 75.0 mmol) was heated at about 60° C. with stirring for about 1 h. The reaction mixture was cooled to ambient temperature and concentrated to dryness under reduced pressure and the resulting material was partitioned between chilled saturated aqueous NaHCO3 (30 mL) and EtOAc (30 mL). The layers were separated and the organic solution was washed with saturated aqueous NaHCO3 solution (30 mL) and brine (30 mL), dried over anhydrous Na2SO4, filtered, and concentrated to dryness under reduced pressure to give 6-chloro-4-(trifluoromethyl)nicotinonitrile (0.67 g, 86%) as a brown liquid: LC/MS (Table 2, Method a) Rt=2.31 min: 1H NMR (CDCl3) δ 8.87 (s, 1H), 7.75 (s, 1H).

Provenance & Evidence