Nitrogen → Tert-butyl 2-oxo-7-azaspiro[3.5]nonane-7-carboxylate

Temperature

15 °C

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.

1. customTo the mixture thus obtained
2. stirringThe mixture was stirred at room temperature overnight
3. additionafter addition
4. stirringTo the reaction mixture stirred in an external ice-bath
5. additionAfter addition
6. stirringthe mixture was stirred at room temperature for 4 h
7. filtrationfiltered
8. customto remove the solid
9. customThe phases were separated
10. extractionThe aqueous phase was extracted with EtOAc
11. washThe combined organic phase was washed with brine
12. dry with materialdried over anhydrous Na2SO4
13. concentrationconcentrated
14. customto give the residue which
15. customwas purified by CombiFlash (40 g silica gel column, EtOAc/Hexane: 0-40%)

ORD record

ord-5da05256bf684a199f4b4b90ac122670

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09226923B2