Acetamide → HCID 58542717, compound

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, a suspension of acetamide (620 mg, 10.5 mmol) and potassium t-butoxide (1.01 g, 10.5 mmol) in DMF (4.5 mL) was heated to 50° C. and stirred for 1.5 hours. It was cooled to 0° C., 5-chloro-2,3-difluoropyridine (450 mg, 3.0 mmol) was added dropwise, DMF (0.45 mL) was further added, and the mixture was stirred at that temperature for 2.5 hours. A saturated ammonium chloride aqueous solution (4.5 mL) and water (4.5 mL) were added to the reaction mixture in that order, and extraction was performed with ethyl acetate (9.0 mL). The aqueous layer was extracted twice with ethyl acetate (9.0 mL), and the combined organic layers were washed with a sodium chloride aqueous solution (4.5 mL) and dried over anhydrous sodium sulfate. A portion (22.1%) of the organic layer was sampled for 1H-NMR quantification, and the solvent was distilled off from the remaining organic layer under reduced pressure. A mixed solvent (7.0 mL) of heptane and t-butyl methyl ether (15:1) was added to the residue to form a suspension, and the suspension was stirred. The precipitated solid was collected by filtration, washed with a mixed solvent (3.5 mL) of heptane and t-butyl methyl ether (15:1), and dried under reduced pressure to obtain the title compound (321 mg, 1.7 mmol).

Provenance & Evidence