反应详情

To a stirred mixture of 3-(difluoromethoxy)-2-methyl-4-(methylsulfonyl)benzoic acid (500 mg, 1.78 mmol) and 5-hydroxy-1-methylpyrazole hydrochloride (288 mg) in anhydrous acetonitrile (10 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (443 mg), triethylamine (360 mg) and dimethylaminopyridine (217 mg) at room temperature. After being stirred for 12 hours, the reaction mixture was concentrated under reduced pressure, and the residue was dissolved in 100 mL of methylene chloride. This solution was washed with 100 mL of water, and the organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was dissolved in 10 mL of anhydrous acetonitrile, and triethylamine (260 mg) and acetone cyanohydrin in a catalytic amount were added, followed by stirring overnight at room temperature. 150 mL of methylene chloride was added to the reaction mixture, followed by extraction with a 1N potassium carbonate aqueous solution, and the aqueous layer was acidified by 2N hydrochloric acid. The obtained acidic aqueous solution was extracted twice with methylene chloride (100 mL), the combined organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography (ethyl acetate:hexane=1:1 to 9:1) to obtain 5-hydroxy-1-methylpyrazol-4-yl 3-(difluoromethoxy)-2-methyl-4-(methylsulfonyl)phenyl ketone as an oil.

1. concentrationthe reaction mixture was concentrated under reduced pressure
2. dissolutionthe residue was dissolved in 100 mL of methylene chloride
3. washThis solution was washed with 100 mL of water
4. dry with materialthe organic layer was dried over anhydrous sodium sulfate
5. distillationthe solvent was distilled off under reduced pressure
6. dissolutionThe residue was dissolved in 10 mL of anhydrous acetonitrile
7. additiontriethylamine (260 mg) and acetone cyanohydrin in a catalytic amount were added
8. stirringby stirring overnight at room temperature
9. addition150 mL of methylene chloride was added to the reaction mixture
10. extractionfollowed by extraction with a 1N potassium carbonate aqueous solution
11. extractionThe obtained acidic aqueous solution was extracted twice with methylene chloride (100 mL)
12. dry with materialthe combined organic layer was dried over anhydrous sodium sulfate
13. distillationthe solvent was distilled off under reduced pressure
14. customThe obtained crude product
15. customwas purified by silica gel column chromatography (ethyl acetate:hexane=1:1 to 9:1)