4-Bromopyrazole → tert-butyl 6-(4-bromo-1H-pyrazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-bromopyrazole (111 mg, 0.755 mmol) in DMF (dry, 2.5 mL) was added NaH (60 wt % in oil, 33 mg, 0.82 mmol) in portions at 0° C. under N2. The mixture was stirred at 0° C. for 15 min, the ice-bath was removed. The mixture was stirred at room temperature for 90 min. tert-butyl 6-((methylsulfonyl)oxy)-2-azaspiro[3.3]heptane-2-carboxylate (200 mg, 0.686 mmol) was added in one portion. The mixture was stirred at room temperature for 1 h, then 80° C. for 18 hrs. The mixture was concentrated in vacuo to give the residue which was dissolved in DCM (30 mL). A saturated solution of NH4Cl (30 mL) was added. The layers were separated. The aqueous phase was extracted with DCM (2×30 mL). The combined organic phase was dried over anhydrous Na2SO4 and then concentrated to give the crude residue which was purified by CombiFlash (40 g silica gel column, Hexane/EtOAc) to afford tert-butyl 6-(4-bromo-1H-pyrazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate (74 mg, 31%) as a white solid.

Provenance & Evidence