反应详情

To a solution of cyclopropylmethyl 6-fluoro-4-methylpyridine-3-carboxylate (3.85 g, 18.4 mmol) obtained in Reference Example 319 and cyclopropylmethanol (1.75 mL, 22.1 mmol) in DMF (30 mL) was added 60% sodium hydride (883 mg, 22.1 mmol) under ice-cooling. After stirring for 30 min, the mixture was stirred at room temperature for 10 min. The reaction was quenched with ice, and the mixture was extracted with ethyl acetate, washed with 10% aqueous potassium carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give cyclopropylmethyl 6-(cyclopropylmethoxy)-4-methylpyridine-3-carboxylate (4.54 g, 94%) as an oil. To a solution of the obtained cyclopropylmethyl 6-(cyclopropylmethoxy)-4-methylpyridine-3-carboxylate (4.54 g, 17.4 mmol) in THF (100 mL) was added lithium aluminum hydride (989 mg, 26.1 mmol) under ice-cooling, and the mixture was stirred for 30 min. To the reaction mixture was slowly added sodium sulfate decahydrate, and the mixture was filtered through celite. The filtrate was concentrated, the residue was dissolved in ethyl acetate, and the solution was applied to basic silica gel column chromatography (ethyl acetate). The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 1:1) to give the title compound (2.87 g, yield 85%).

1. temperaturecooling
2. filtrationthe mixture was filtered through celite
3. concentrationThe filtrate was concentrated
4. dissolutionthe residue was dissolved in ethyl acetate
5. customThe solvent was evaporated under reduced pressure
6. customthe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 1:1)