Ammonia → 2-bromo-N-(2,6-dimethyl-4-trifluoromethyl-3-pyridyl)acetamide

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Reaction Steps

3-Amino-2,6-dimethyl-4-trifluoromethylpyridine dihydrochloride (15.60 g, 59.30 mmol) was dissolved in methanol (100 mL). In an ice bath, an ammonia-saturated methanol solution (300 mL) was added, and the mixture was rendered uniform. The reaction mixture was extracted from chloroform-water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in dichloromethane (200 mL), and subsequent to the addition of N,N-dimethylaniline (10.80 g, 89.12 mmol), a solution of bromoacetyl bromide (15.52 g, 76.90 mmol) in dichloromethane (40 mL) was added dropwise while stirring the mixture in an ice bath. The mixture was stirred at room temperature for two hours, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (silica gel: 400 g; developer: hexane:acetone=10:1→4:1→3:1). Recrystallization from ethyl acetate and hexane afforded the title compound (17.68 g, 96%) as colorless needles.

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