Reaction #674299

Reaction equation

tert-butyl 4-methylenepiperidine-1-carboxylate

2,2,2-trichloroacetyl chloride

NH4Cl

N2

→

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

Yield 15.0%

Solvents

t-BuOMe

DME

Conditions

Workup

1. 1
   OtherTo 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
   Filtrationfiltered
8. 8
   Otherto remove the solid
9. 9
   OtherThe phases were separated
10. 10
    ExtractionThe aqueous phase was extracted with EtOAc
11. 11
    WashThe combined organic phase was washed with brine
12. 12
    Dryingdried over anhydrous Na2SO4
13. 13
    Concentrationconcentrated
14. 14
    Otherto give the residue which
15. 15
    Otherwas purified by CombiFlash (40 g silica gel column, EtOAc/Hexane: 0-40%)

Procedure

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.

Source