Chlorosuccinimide → 4-Amino-3-chloro-5-fluorobenzonitrile

Participants

Reaction Steps

A solution of 4-amino-3-fluorobenzonitrile (25.13 g, 185 mmol) and NCS (24.65 g, 185 mmol) in acetonitrile (500 mL) was stirred at 86° C. (reflux) for 5 h. LCMS showed ˜17% of starting material remained. Additional NCS (0.2 eq) was added and the reaction was stirred for 1 h. The reaction was partly concentrated and the residue was partitioned between 5% NaOH (100 mL) and EtOAc. The aqueous layer was back extracted with EtOAc. The organic extracts were dried over Na2SO4 and concentrated to a pink solid. The NMR spectrum showed some of the succinimate side product still remained. The crude product was washed with H2O and air dried to give the desired product as a beige solid. This product was used in the next step without any further purification. MS (m/z) 171.1 (M+H+).

Provenance & Evidence