反应详情

To a solution wherein 6-amino-5-chloro-1,1,3,3-tetrafluoro-1,3-dihydroisobenzofuran (2.41 g, 10.0 mmol) is in acetic acid (30 ml), a nitrosylsulfuric acid solution prepared from sodium nitrite (760 mg, 11.0 mmol) and concentrated sulfuric acid (5.5 ml) was added dropwise at 10 to 15° C. over a period of about 10 minutes. The reaction solution was added dropwise to a mixture consisting of sodium acetate (7 g) and a 1:1 mixture (1.45 g) of methyl 2,3-dicyanopropionate and ethyl 2,3-dicyanopropionate, and 50 ml of water under vigorous stirring at room temperature and further stirred for 30 minutes. After reaction solution was extracted with chloroform, the organic layer was washed with a saturated sodium hydrogencarbonate solution, then dried over anhydrous magnesium sulfate and concentrated under reduced pressure until the amount of the solution became about 20 ml. 5 ml of ammonia water was added to the resulting solution and stirred at room temperature for 2 hours. After water was poured into the solution, the solution was extracted with chloroform, the organic layer was washed with a 1N hydrochloric acid solution and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography to give 1.0 g of 5-amino-1-(6-chloro-1,1,3,3-tetrafluoro-1,3-dihydroisobenzofuran-5-yl)-3-cyanopyrazole.

1. additionwas added dropwise at 10 to 15° C. over a period of about 10 minutes
2. additionThe reaction solution was added dropwise to a mixture
3. customAfter reaction solution
4. extractionwas extracted with chloroform
5. washthe organic layer was washed with a saturated sodium hydrogencarbonate solution
6. dry with materialdried over anhydrous magnesium sulfate
7. concentrationconcentrated under reduced pressure until the amount of the solution
8. addition5 ml of ammonia water was added to the resulting solution
9. stirringstirred at room temperature for 2 hours
10. additionAfter water was poured into the solution
11. extractionthe solution was extracted with chloroform
12. washthe organic layer was washed with a 1N hydrochloric acid solution
13. dry with materialdried over anhydrous magnesium sulfate
14. distillationThe solvent was distilled off under reduced pressure