Citric Acid → HCID 67342382, compound

Participants

Reaction Steps

To a solution of the compound obtained in Reference Example 63(1) (295 mg) in dichloromethane (10 mL) were added oxalyl chloride (253 μL) and a drop of N,N-dimethylformamide, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo to give crude 2-(2-bromo-5-nitrophenoxy)-2-methylpropionyl chloride. To a solution of 2-amino-5-bromo-3-methylpyridine (727 mg) in tetrahydrofuran (20 mL) was added dropwise 1M lithium bis(trimethylsilyl)amide-tetrahydrofuran solution (3.88 mL) over a period of one minute under cooling in dry ice-acetone bath under argon atmosphere. The mixture was stirred at the same temperature for 5 minutes. Thereto was added quickly a solution of 2-(2-bromo-5-nitrophenoxy)-2-methylpropionyl chloride in tetrahydrofuran (10 mL), and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added an aqueous citric acid solution, and the mixture was basified with an aqueous saturated sodium hydrogencarbonate solution and extracted with ethyl acetate. The organic layer was washed successively with water and brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on NH-silica gel (Chromatorex NH-silica gel; solvent; n-hexane/ethyl acetate=19/1→3/1) to give N-(5-bromo-3-methylpyridin-2-yl)-2-(2-bromo-5-nitrophenoxy)-2-methylpropionamide (599 mg) as a colorless powder.

Provenance & Evidence