反应详情

In 50 ml of DMF were suspended 8.5 g (0.05 mole) of the 3-ethoxycarbonyl-5-hydroxy-1-methylpyrazole synthesized in Reference Example 3 and 10.5 g (0.08 mole) of potassium carbonate. In this suspension being stirred at room temperature was placed 2.3 g (0.08 mole) of paraformaldehyde, followed by stirring at the same temperature for 1 hour. Then, 20.9 g (0.15 mole) of potassium carbonate was added. Therein was blown 8.6 g (0.10 mole) of chlorodifluoromethane. The reaction mixture was stirred at room temperature for 2 hours to give rise to a reaction. After the reaction, 200 ml of ethyl acetate and 200 ml of water were added. The organic layer, which appeared by phase separation, was separated. The aqueous layer was subjected to re-extraction with 50 ml of ethyl acetate three times. The organic layers were combined and washed with 50 ml of water, 30 ml of a saturated aqueous ammonium chloride solution and 30 ml of a saturated aqueous sodium chloride solution in this order. The resulting organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to obtain 24.3 g (purity: 42.2%, yield: 82.0%) of a crude solution of title compound. The crude solution was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1) to obtain a title compound as white crystals.

1. stirringby stirring at the same temperature for 1 hour
2. stirringThe reaction mixture was stirred at room temperature for 2 hours
3. customto give rise
4. customto a reaction
5. additionwere added
6. customThe organic layer, which appeared by phase separation
7. customwas separated
8. extractionThe aqueous layer was subjected to re-extraction with 50 ml of ethyl acetate three times
9. washwashed with 50 ml of water, 30 ml of a saturated aqueous ammonium chloride solution and 30 ml of a saturated aqueous sodium chloride solution in this order
10. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
11. concentrationconcentrated under reduced pressure