Sodium periodate → 1-Tert-butyl 4-ethyl 4-(2-oxobutyl)piperidine-1,4-dicarboxylate

HRID 1848493Notes

Reaction equation

HRID 1848493 reaction equation
C=[C:2]([CH2:22][CH3:23])[CH2:3][C:4]1([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.I([O-])(=O)(=O)=[O:25].[Na+]>CC(C)=O.O.O[Os](O)(O)(O)(=O)=O.[K]>[O:25]=[C:2]([CH2:22][CH3:23])[CH2:3][C:4]1([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])[CH2:6][CH2:5]1

Participants

6

Reactant 2

HCID 23667635Sodium periodateHCID 867095031-Tert-butyl 4-ethyl 4-(2-methylenebutyl)piperidine-1,4-dicarboxylate

Product 1

HCID 867095041-Tert-butyl 4-ethyl 4-(2-oxobutyl)piperidine-1,4-dicarboxylate

Reagents, catalysts & solvents 3

HCID 178506626HCID 178506626, compoundCatalyst2×HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

Potassium tetrahydroxydioxidoosmium (0.041 g, 0.111 mmol) was added to a solution of 1-tert-butyl 4-ethyl 4-(2-methylenebutyl)piperidine-1,4-dicarboxylate (1.0 g, 3.07 mmol) in acetone (20 mL) and water (20 mL) and stirred for 10 min. Solid sodium periodate (2.62 g, 12.26 mmol) was added in four portions during 1 hour and the reaction temperature was maintained below 40° C. using an ice-bath. The resulting mixture was stirred for 1 hour at room temperature. At this point LCMS showed incomplete reaction. Another 0.036 eq. of potassium tetrahydroxydioxidoosmium (0.041 g, 0.111 mmol) was added and the mixture was then stirred at rt for 2 hours. LCMS after 2 hours showed completion of the reaction. The suspension was filtered and filtrate was concentrated to remove acetone, and the aqueous layer was extracted with DCM (15 mL×3). The combined organic layers were washed with 10% Na2S2O3 solution (20 ml×2), dried over anhydrous Na2SO4, filtered, then concentrated to get the crude product which was purified by silica gel column chromatography (80 g RediSep Gold column) using (0-35) % EtOAc/Hexanes as mobile phase and the title compound was isolated.

Workup

  1. temperaturethe reaction temperature was maintained below 40° C.
  2. stirringThe resulting mixture was stirred for 1 hour at room temperature
  3. customreaction
  4. stirringthe mixture was then stirred at rt for 2 hours
  5. waitLCMS after 2 hours showed
  6. customcompletion of the reaction
  7. filtrationThe suspension was filtered
  8. concentrationfiltrate was concentrated
  9. customto remove acetone
  10. extractionthe aqueous layer was extracted with DCM (15 mL×3)
  11. washThe combined organic layers were washed with 10% Na2S2O3 solution (20 ml×2)
  12. dry with materialdried over anhydrous Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto get the crude product which
  16. customwas purified by silica gel column chromatography (80 g RediSep Gold column)

Sources & evidence

ORD record
ord-7fc5ad005b7b4bc18ecc0b82eb269eda
Source dataset
uspto-grants-2015_02
Patent number
US08952166B2

Reaction notes

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