反応 #674294

反応方程式

NH4Cl

tert-butyl 6-((methylsulfonyl)oxy)-2-azaspiro[3.3]heptane-2-carboxylate

4-bromopyrazole

NaH

→

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

収率 31.5%

溶媒

DCM

DMF

反応条件

後処理

1. 1
   その他the ice-bath was removed
2. 2
   workup.ADDITIONwas added in one portion
3. 3
   workup.STIRRINGThe mixture was stirred at room temperature for 1 h
4. 4
   workup.WAIT80° C. for 18 hrs
5. 5
   濃縮The mixture was concentrated in vacuo
6. 6
   その他to give the residue which
7. 7
   その他The layers were separated
8. 8
   抽出The aqueous phase was extracted with DCM (2×30 mL)
9. 9
   乾燥The combined organic phase was dried over anhydrous Na2SO4
10. 10
    濃縮concentrated
11. 11
    その他to give the crude residue which
12. 12
    その他was purified by CombiFlash (40 g silica gel column, Hexane/EtOAc)

実験手順

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.

出典