Dimethylformamide → 4,6-Dichloronicotinamide

Participants

Reaction Conditions

Reaction Steps

4,6-Dichloro-nicotinic acid (10.3 g, 53.4 mmol) was suspended in CH2Cl2 (200 mL). Oxalyl chloride (14 mL, 158 mmol) was added and the reaction was placed in an ice bath. DMF (1.0 mL) was added and the reaction was fitted with an air cooled condenser. The reaction was stirred for 3 h and allowed to warm to 25° C. The volatiles were removed in vacuo and the crude residue was resuspended in THF (200 mL) and cooled to 0° C. To this stirred suspension was added concentrated aqueous ammonia (75 mL) dropwise and the reaction was allowed to stir for 1 h. The volatiles were removed and the crude was redissolved in EtOAc and poured into brine. The aqueous phase was separated and extracted twice with EtOAc. The organic layers were combined, dried (Na2SO4), decanted and concentrated to afford 4,6-dichloro-nicotinamide as a beige solid (7.27 g, 71%).

Provenance & Evidence