1,2-Dibromoethane → 1-(1-methyl-1H-pyrazol-5-yl)cyclopropane-1-carbonitrile

Participants

Reaction Steps

To a solution of 2-(1-methyl-1H-pyrazol-5-yl)acetonitrile (65 mg, 0.54 mmol) in N,N-dimethylformamide (3 mL) were added potassium t-butoxide (1M in tetrahydrofuran, 1.2 mL, 1.2 mmol) and 1,2-dibromoethane (130 μL, 1.5 mmol). The reaction mixture was stirred for 16 h at room temperature then at 70° C. for 7 h. The mixture was cooled to room temperature, quenched with water (2 mL) and extracted with diethyl ether (3×10 mL). The combined organic layers were washed with brine (3 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was dried under high vacuum. A solution of the residue and 1,2-dibromoethane (65 μL, 0.75 mmol) in N,N-dimethylformamide (0.5 mL) was added dropwise to a suspension of sodium hydride (washed, 23 mg, 1.0 mmol) in N,N-dimethylformamide (1.0 mL) at room temperature. After 16 h, additional portions of 1,2-dibromoethane (25 μL, 0.29 mmol) and sodium hydride (8 mg, 0.35 mmol) were added to the reaction mixture at room temperature. After 2 h, the mixture was quenched with water (3 mL) and extracted with diethyl ether (2×10 mL). The combined organic layers were washed with brine (3 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was dried under high vacuum to yield the volatile 1-(1-methyl-1H-pyrazol-5-yl)cyclopropanecarbonitrile (20.1 mg, 25%) as a brown oil. 1H NMR (500 MHz, CDCl3) δ 1.34-1.41 (m, 2H), 1.70-1.76 (m, 2H), 4.03 (s, 3H), 6.10 (d, 1H), 7.39 (d, 1H).

Provenance & Evidence