反应详情

To a solution wherein 5-chloro-1,1,3,3-tetrafluoro-1,3-dihydroisobenzofuran-6-yl-hydrazine (900 mg, 3.5 mmol) and disodium ethylenediaminetetraacetate (1 mg) are in methanol (6 ml), 2-chloroacrylonitrile (919 mg, 10.5 mmol) was added dropwise at 60° C., and under reflux for 8 hours, subsequently concentrated sulfuric acid (0.5 ml, 9.4 mmol) was added to the solution and was further heated under reflux for 6 hours. After the reaction solution was allowed to cool, anhydrous sodium carbonate (1.17 g, 10.5 mmol) was added to the reaction solution, stirred for 4 hours, and had the solvent distilled off under reduced pressure. Subsequently, water was added to the residue, the solution was extracted with ethyl acetate, and the organic layer was 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 400 mg of 5-amino-1-(6-chloro-1,1,3,3-tetrafluoro-1,3-dihydroisobenzofuran-5-yl)-pyrazole.

1. temperatureunder reflux for 8 hours
2. temperaturewas further heated
3. temperatureunder reflux for 6 hours
4. temperatureto cool
5. distillationdistilled off under reduced pressure
6. additionSubsequently, water was added to the residue
7. extractionthe solution was extracted with ethyl acetate
8. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
9. distillationThe solvent was distilled off under reduced pressure