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

Temperature

0 °C

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.

1. customthe ice-bath was removed
2. additionwas added in one portion
3. stirringThe mixture was stirred at room temperature for 1 h
4. wait80° C. for 18 hrs
5. concentrationThe mixture was concentrated in vacuo
6. customto give the residue which
7. customThe layers were separated
8. extractionThe aqueous phase was extracted with DCM (2×30 mL)
9. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
10. concentrationconcentrated
11. customto give the crude residue which
12. customwas purified by CombiFlash (40 g silica gel column, Hexane/EtOAc)

ORD record

ord-9cb8e80db79d4a148a9bdeb116705f41

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09226923B2