1,1,3-Trichloroacetone → 2-(Dichloromethyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine

Beteiligte Stoffe

Reaktionsschritte

To a solution of 5-(Trifluoromethyl)pyridin-2-amine (12.9 g) was dissolved in dimethoxyethane (150 mL) was added 1,1,3-trichloroacetone (12.7 mL) at room temperature, and the mixture was stirred overnight. The precipitated solid was collected, and suspended in ethanol (50 mL), and the mixture was heated under reflux for 3 hr. After allowing to cool to room temperature, the solvent was evaporated under reduced pressure, saturated aqueous sodium hydrogen carbonate was added to the residue, and the mixture was extracted with ethyl acetate-tetrahydrofuran (1:1, volume ratio). The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2, volume ratio) to give 2-(dichloromethyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine (10.3 g) as a white solid. The obtained solid was suspended in a mixed solvent of water (100 mL) and tetrahydrofuran (20 mL), and calcium carbonate (8.0 g) was added to the mixture at room temperature, and the mixture was stirred at 100° C. for 1 hr. The mixture was allowed to cool to room temperature, the insoluble material was filtered off, and the filtrate was extracted with ethyl acetate. The extract was dried over magnesium sulfate, and concentrated under reduced pressure to give a white solid. The residue was washed with diisopropyl ether to give the title object compound (7.3 g, 43%) as white crystals.

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