Dimethylformamide → 6-Chloronicotinoyl Chloride

Participants

Reaction Conditions

Reaction Steps

A carboxylic acid, e.g., 6-Chloronicotinic acid (3.151 g, 20 mmol) was dissolved in dry DCM. The mixture was cooled down to 0° C. Oxalyl chloride (2.58 mL, 30 mmol) followed by DMF (77 μL) were added. The mixture was stirred at 0° C. for 1 h 30, then at RT overnight. The solvents were evaporated. The crude product was dissolved in toluene and the solvents were evaporated again to give the corresponding acid chloride (XVIII*), e.g., 6-chloronicotinoyl chloride (2.886 g, 82% yield). It was dissolved in benzene (50 mL) and AlCl3 (5.248 g, 39.4 mmol) was added. The mixture was stirred overnight at 80° C. After cooling down to RT, water was added. The two phases were separated and the aqueous layer was extracted with two portions of ethyl acetate. Combined organic layers were washed with brine and dried over MgSO4, filtrated and concentrated to give the desired product (XIX*), e.g., (6-chloropyridin-3-yl)(phenyl)methanone as a yellowish oil (3.884 g, 67% yield). It was used in the next step without further purification.

Provenance & Evidence