4-Methylpyrazole → tert-butyl 1-(4-methyl-1H-pyrazol-1-yl)cyclopropanecarboxylate

Participants

Reaction Conditions

Reaction Steps

Into a 25 mL round bottom flask were added sodium hydride (60% dispersion in mineral oil, 164.3 mg, 4.1 mmol) and anhydrous tetrahydrofuran (8 mL). The mixture was cooled with an ice-water bath before a solution of 4-methylpyrazole (204.2 mg, 2.487 mmol) in anhydrous tetrahydrofuran (2 mL) was added. The mixture was stirred in the ice-water bath for 30 minutes before tert-butyl 2,4-dibromobutanoate (0.48 mL, 2.2 mmol) was added dropwise at 0° C. The reaction mixture was stirred at 0° C. for 30 minutes and then at room temperature for 18 h. The solvent was removed under reduced pressure and water and ethyl acetate were added to the residue. The layers were separated and the aqueous layer was extracted with ethyl acetate (3×). The combined organics were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via flash chromatography (0-50% ethyl acetate in heptanes) to afford tert-butyl 1-(4-methyl-1H-pyrazol-1-yl)cyclopropanecarboxylate (218 mg, 44%). 1H NMR (400 MHz, CDCl3) δ 1.33 (s, 9H), 1.45-1.51 (m, 2H), 1.61-1.67 (m, 2H)H), 1.98-2.01 (m, 3H)H), 7.21 (s, 1H), 7.23-7.26 (m, 1H).

Provenance & Evidence