Dimethylformamide → HCID 46941716, compound

Participants

Reaction Steps

Thionyl chloride (100 mL) was added to 4-chloronicotinic acid (22.4 g), and the mixture was stirred with heating under reflux for 4 hr, and concentrated under reduced pressure. To a solution (300 mL) of the residue in methylene chloride were added N,O-dimethylhydroxylamine hydrochloride (13.8 g) and triethylamine (60 mL), and the mixture was stirred at room temperature for 5 hr. Water was added to the reaction mixture, and the reaction mixture was extracted with methylene chloride. The extract was dried over sodium sulfate, and concentrated under reduced pressure. To a solution (300 mL) of the residue in tetrahydrofuran was added a 3.0 M solution (54 mL) of methylmagnesium chloride in ether at −78° C. and the mixture was stirred under nitrogen atmosphere at room temperature for 10 hr. The reaction mixture was acidified with aqueous sodium carbonate solution to pH=9, and extracted with ethyl acetate. The extract was dried over sodium sulfate, and concentrated under reduced pressure to give a colorless oil. To a mixture of the obtained oil, ethyl mercaptoacetate (21 mL) and anhydrous N,N-dimethylformamide (200 mL) was added sodium hydride (60%, oily, 7.34 g) at 5° C. over 30 min, and the mixture was stirred at 5° C. for 20 min then at room temperature for 18 hr. Water was added to quench the reaction, and the reaction mixture was extracted with ethyl acetate. The extract was dried over sodium sulfate, and concentrated under reduced pressure. The obtained solid was recrystallized from petroleum ether/ethyl acetate to give the title object compound (5.45 g, 17%) as a white solid.

Provenance & Evidence