Triethylamine → 4-Amino-2-chloro-3-fluorobenzonitrile

Participants

Reaction Steps

To a solution of hydroxylamine hydrochloride (336 mg, 4.84 mmol) in water (1.2 mL) was added 4-amino-2-chloro-3-fluorobenzaldehyde (73A) (0.800 g, 4.61 mmol) and pyridine (2.5 mL). After stirring at rt for 1 h, copper (II) sulfate pentahydrate (230 mg, 0.922 mmol) was added followed by a solution of triethylamine (1.40 mL, 9.68 mmol) in CH2Cl2 (2.5 mL). To the resulting dark green reaction mixture was then added a solution of DCC (1.14 g, 5.53 mmol) in CH2Cl2 (10 mL) and the reaction was stirred for 2 h. Formic acid (1 mL) was added and the reaction was stirred for 20 min, filtered through celite, and concentrated. The resulting residue was purified via silica gel chromatography eluting with 20-30% EtOAc/hexane to provide the title compound (0.780 g) as a light brown solid.

Provenance & Evidence