반응 #674299

반응 방정식

tert-butyl 4-methylenepiperidine-1-carboxylate

2,2,2-trichloroacetyl chloride

NH4Cl

N2

→

tert-butyl 2-oxo-7-azaspiro[3.5]nonane-7-carboxylate

수율 15.0%

용매

t-BuOMe

DME

반응 조건

후처리

1. 1
   기타To the mixture thus obtained
2. 2
   workup.STIRRINGThe mixture was stirred at room temperature overnight
3. 3
   workup.ADDITIONafter addition
4. 4
   workup.STIRRINGTo the reaction mixture stirred in an external ice-bath
5. 5
   workup.ADDITIONAfter addition
6. 6
   workup.STIRRINGthe mixture was stirred at room temperature for 4 h
7. 7
   여과filtered
8. 8
   기타to remove the solid
9. 9
   기타The phases were separated
10. 10
    추출The aqueous phase was extracted with EtOAc
11. 11
    세척The combined organic phase was washed with brine
12. 12
    건조dried over anhydrous Na2SO4
13. 13
    농축concentrated
14. 14
    기타to give the residue which
15. 15
    기타was purified by CombiFlash (40 g silica gel column, EtOAc/Hexane: 0-40%)

실험 절차

To a flame-dried RB flask with tert-butyl 4-methylenepiperidine-1-carboxylate (2.96 g, 15 mmol, 1.0 equiv) and Zn/Cu couple (6.54 g, 172.5 mmol, 11.5 equiv) under vacuum, t-BuOMe (60 mL) was charged and refilled the flask with N2 balloon. To the mixture thus obtained stirred at 15° C., a solution of 2,2,2-trichloroacetyl chloride in DME (20 mL) was added dropwise. The mixture was stirred at room temperature overnight after addition. To the reaction mixture stirred in an external ice-bath, a saturated solution of NH4Cl (60 mL) was added slowly and carefully (especially the first few drops). After addition, the mixture was stirred at room temperature for 4 h, filtered to remove the solid. The phases were separated. The aqueous phase was extracted with EtOAc. The combined organic phase was washed with brine, dried over anhydrous Na2SO4, concentrated to give the residue which was purified by CombiFlash (40 g silica gel column, EtOAc/Hexane: 0-40%) to afford 619 mg (15%) of tert-butyl 2-oxo-7-azaspiro[3.5]nonane-7-carboxylate.

출처