反应详情

温度

10 °C

Into a 4-neck 2 L round bottom flask, previously dried with a heat gun under high vacuum, was added dimethylsulfoxide (175 mL). The flask was placed in a 10° C. bath and sodium hydride (60% oil dispersion, 17.0 g, 300 mmol) was added portionwise with stirring under nitrogen. The resulting suspension was stirred for 10 min before a solution of 2-(4-chloro-1H-pyrazol-1-yl)acetonitrile (10.0 g, 70.6 mmol) and 1,2-dibromoethane (18.3 mL, 213 mmol) in dimethylsulfoxide (175 mL) was added dropwise over a period of 30 min. The internal temperature was kept between 13 and 20° C. during the addition process. The reaction mixture was stirred for 5.5 h while keeping the internal temperature at or below 20° C., followed by stirring for an additional 1 h at room temperature. The mixture was cooled to 10° C., and then a saturated aqueous solution of ammonium chloride (600 mL) was slowly added. The mixture was stirred at 10° C. for 15 min, then extracted with ethyl acetate (1000 mL×3). The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via flash chromatography (10-100% dichloromethane in hexanes), and the residue was crystallized from a mixture of hexanes/diethyl ether to afford 1-(4-chloro-1H-pyrazol-1-yl)cyclopropanecarbonitrile (7.654 g). 1H NMR (400 MHz, CDCl3) δ 1.80-1.82 (m, 4H) 7.47 (d, 1H) 7.62 (d, 1H); MS (EI+) (M+) 167; GCMS retention time 1.64 minutes (Method O).

1. customInto a 4-neck 2 L round bottom flask, previously dried with a heat gun under high vacuum
2. additionwas added dimethylsulfoxide (175 mL)
3. customwas placed in a 10° C.
4. additionwas added dropwise over a period of 30 min
5. customwas kept between 13 and 20° C. during the addition process
6. stirringThe reaction mixture was stirred for 5.5 h
7. custombelow 20° C.
8. stirringby stirring for an additional 1 h at room temperature
9. stirringThe mixture was stirred at 10° C. for 15 min
10. extractionextracted with ethyl acetate (1000 mL×3)
11. washThe combined organics were washed with brine
12. dry with materialdried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customThe crude material was purified via flash chromatography (10-100% dichloromethane in hexanes)
16. customthe residue was crystallized from a mixture of hexanes/diethyl ether