反应详情

To a solution of 2-oxazolydone (20.8 g) in tetrahydrofuran (750 ml) was added n-butyllithium (1.56 M hexane solution, 153 ml) at −78° C. and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added a solution of cyclopropanecarbonyl chloride (25 g) in tetrahydrofuran (50 ml) at −78° C. over 30 minutes. The mixture was stirred for 14 hours while gradually raising the temperature to room temperature. The reaction mixture was poured into ice-water and the mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The extract was concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate (1:1)) to give white crystals (26 g). A mixture of the obtained white crystals (10 g), ethyl bromoacetate (21.5 ml) and zinc powder (25.3 g) in tetrahydrofuran (300 ml) was ultrasonicated for 2 hours and heated under reflux for 2 hours. To the reaction mixture was added 10% hydrochloric acid and the insoluble material was filtered off through Celite. The filtrate was extracted with ethyl acetate, and the extract was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The extract was concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate (1:1)) to give ethyl 3-cyclopropyl-3-oxopropionate (5.7 g) as a yellow oil. Subsequently, the title compound was prepared from 2-chlorobenzaldehyde, 3-aminopyrazole and ethyl 3-cyclopropyl-3-oxopropionate in the same manner as in Example 275.

1. customwas ultrasonicated for 2 hours
2. temperatureheated
3. temperatureunder reflux for 2 hours
4. filtrationthe insoluble material was filtered off through Celite
5. extractionThe filtrate was extracted with ethyl acetate
6. washthe extract was washed with a saturated aqueous sodium chloride solution
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationThe extract was concentrated under reduced pressure
9. customthe obtained residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate (1:1))