Dichloromethane → 5-Amino-1-(2-chloro-4-fluorophenyl)-1H-pyrazole-4-carbonitrile

Participants

Reaction Conditions

Reaction Steps

2-Chloro-4-fluorophenyl hydrazine hydrochloride (CAS 497959-29-2) (25.0 g, 126.9 mmol) was partitioned between DCM (250 mL) and 2M NaOH (100 mL). The organic phase was separated and washed sequentially with water (2×150 mL) and brine (150 mL), dried over MgSO4 and evaporated to give the free base. This oil was dissolved in MeOH (200 mL) under nitrogen at −5° C. and 2-(ethoxymethylene)malononitrile (15.5 g, 127 mmol) was added portionwise. The resulting mixture was stirred at 0° C. for 2 hours then at reflux for a further 2 hours. After cooling, the mixture was evaporated to provide 5-amino-1-(2-chloro-4-fluorophenyl)-1H-pyrazole-4-carbonitrile (28.9 g).

Provenance & Evidence