Реакция #674299

Уравнение реакции

tert-butyl 4-methylenepiperidine-1-carboxylate

2,2,2-trichloroacetyl chloride

NH4Cl

N2

→

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

Выход 15.0%

Растворители

t-BuOMe

DME

Условия реакции

Обработка

1. 1
   ДругоеTo 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
   Фильтрацияfiltered
8. 8
   Другоеto remove the solid
9. 9
   ДругоеThe phases were separated
10. 10
    ЭкстракцияThe aqueous phase was extracted with EtOAc
11. 11
    ПромывкаThe combined organic phase was washed with brine
12. 12
    Сушкаdried over anhydrous Na2SO4
13. 13
    Концентрированиеconcentrated
14. 14
    Другоеto give the residue which
15. 15
    Другоеwas purified by CombiFlash (40 g silica gel column, EtOAc/Hexane: 0-40%)

Методика

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.

Источник