1,2-Dibromoethane → 1-(4-Chloropyrazol-1-yl)cyclopropane-1-carbonitrile

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Reaction Conditions

Reaction Steps

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).

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