Hydrochloric Acid → HCID 19365505, compound

Participants

Reaction Steps

To a mixed solution of 121 g of sodium carbonate and 400 ml of water was added dropwise 77.1 g of 1,1-dibromo-3,3,3-trifluoroacetone at such a rate that the temperature of the reaction mixture became not higher than 55° C. After completion of the dropwise addition, the mixture was stirred at room temperature for 30 minutes, followed by adding 500 ml of water and then 40 g of 2-amino-2-(2,4-difluorophenyl)acetamide, and the reaction was allowed to proceed at 60° C. for 2 hours. After completion of the reaction, the reaction mixture was cooled to 10° C. or lower, made acidic by adding 80 ml of concentrated hydrochloric acid at the same temperature, and extracted with ethyl acetate. The organic layer was washed with water and then saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane/ethyl acetate=4:1), which afforded 23.3 g (yield, 39%) of the desired compound, 3-(2,4-difluorophenyl)-6-trifluoromethyl-2-oxo-1,2-dihydropyrazine (compound 1-1004; m.p., 178.9° C.). The continued elution with the above solvent system gave 13.2 g of the configurational isomer, 3-(2,4-difluorophenyl)-5-trifluoromethyl-2-oxo-1,2-dihydropyrazine (m.p., 164.6° C.).

Provenance & Evidence