Pyrazole → HCID 89853540, compound

Participants

Reaction Steps

Into a 50 mL round bottom flask was added sodium hydride (60% dispersion in mineral oil, 452 mg, 11 mmol) and anhydrous tetrahydrofuran (18 mL). To the mixture was added pyrazole (511.6 mg, 7.515 mmol) and anhydrous tetrahydrofuran (1 mL). The mixture was stirred at room temperature for 2 h and then cooled to 0° C. Ethyl 1-bromocyclobutanecarboxylate (1.3 mL, 7.5 mmol) was added dropwise. The reaction mixture was stirred at 0° C. for 45 minutes and at room temperature over three days. HMPA (1.35 mL, 7.5 mmol) was added and the mixture was stirred at room temperature for 2 h. The reaction mixture was warmed to 70° C. for 2 h followed by the addition of N,N-dimethylformamide (4 mL). The reaction mixture was stirred at 70° C. for another 2 h before more N,N-dimethylformamide (2 mL) was added and then stirred at 70° C. for 18 h. The solvent was removed under reduced pressure. To the residue was added water and extracted with a mixture of heptanes and ethyl acetate (3×). The combined organics were dried over magnesium sulfate, filtered and concentrated under reduced pressure. Flash chromatography (0-40% ethyl acetate in heptanes) provided impure ethyl 1-(1H-pyrazol-1-yl)cyclobutanecarboxylate (688 mg), which was used without further purification.

Provenance & Evidence