Dimethylformamide → 4-(4-Chloro-2-fluorophenyl)-2-methylnicotinamide

Participants

Reaction Conditions

Reaction Steps

4-(4-Chloro-2-fluorophenyl)-2-methylnicotinic acid (9 g, 33.9 mmol) (previous described in Example 16, Part E) was taken in DCM (50 mL) and cooled to 0° C. The solution was treated with oxalyl chloride (14.83 mL, 169 mmol) followed by slow addition of DMF (1 mL). The mixture was heated at 40° C. for 3 h. After cooling, the volatiles were removed under reduced pressure. The residue taken up in DCM (25 mL) was cooled to 0° C., and TEA (22.08 mL, 158 mmol) and ammonium chloride (16.94 g, 317 mmol) were added slowly. After stirring at room temperature for 1 h, the reaction mixture was washed with saturated aqueous NaHCO3 (10 mL), water (10 mL), and brine (10 mL). The organic layer was separated and dried with Na2SO4 to afford the 4-(4-chloro-2-fluorophenyl)-2-methylnicotinamide (3.5 g, 13.2 mmol, 42% crude yield) as a brown solid. The material was carried forward without further purification. LC/MS (ESI) m/e 264.4 [(M)+, calcd for C13H10ClFN2O 264.0] LC/MS retention time (method C): tR=1.58 min.

Provenance & Evidence