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

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).

1. waitat 70° C. for 7 h
2. temperatureThe mixture was cooled to room temperature
3. customquenched with water (2 mL)
4. extractionextracted with diethyl ether (3×10 mL)
5. washThe combined organic layers were washed with brine (3 mL)
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was dried under high vacuum
10. waitAfter 16 h
11. waitAfter 2 h
12. customthe mixture was quenched with water (3 mL)
13. extractionextracted with diethyl ether (2×10 mL)
14. washThe combined organic layers were washed with brine (3 mL)
15. dry with materialdried over magnesium sulfate
16. filtrationfiltered
17. concentrationconcentrated under reduced pressure
18. customThe residue was dried under high vacuum

ORD record

ord-34496029542a47ae9fd8ee703d86de5b

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296745B2