Ozone → Benzyl (5R)-5-methyl-2-oxopiperidine-1-carboxylate

HRID 1780001Notes

Reaction equation

HRID 1780001 reaction equation
O=[O+][O-].[CH3:4][C@H:5]([CH2:18][CH2:19][CH:20]=C(C)C)[CH2:6][NH:7][C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9].CC(C)=[O:26].OS(O)(=O)=O.O=[Cr](=O)=O>O=O.C(Cl)Cl.CC(C)=O>[CH3:4][C@H:5]1[CH2:6][N:7]([C:8]([O:10][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[O:9])[C:20](=[O:26])[CH2:19][CH2:18]1

Participants

7

Reactant 3

HCID 24823OzoneHCID 22872580(R)-N-Cbz-2,6-dimethyl-5-hepten-1-amineHCID 131709961Jones' reagent

Product 1

HCID 22872605Benzyl (5R)-5-methyl-2-oxopiperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 977OxygenSolventHCID 6344DichloromethaneSolvent

Procedure

Ozone in oxygen (4%) was passed through a solution of 2-(R),6-dimethyl-1-benzyloxycarbonylamino-5-heptene (9.8 g) in 150 mL of methylene chloride at -78° C. until the blue color persisted. Nitrogen was then bubbled for 15 mins. 16 mL of dimethyl sulfide was added and the mixture was stirred 1 hr as it warmed to room temperature and then concentrated to give a residual oil. This was taken up in 100 mL of acetone and cooled in ice bath. Jones reagent was added dropwise until orange color was sustained. After stirring 30 mis, 4 mL of isoprpopyl alcohol was added and the mixture was stirred for an additional 15 mins. Solvent was then removed in vacuo and the residue was stirred with water and ethyl acetate. The organic phase was separated and the aqueous phase was extracted with ethyl acetate. The combined ethyl acetate extracts were dried over anhydrous magnesium sulfate and the solvent was removed in vacuo. The resulting residue was purified on silica gel using first 10% ethyl acetate in hexane as solvent to give 2.0 g of 5(R)-methyl-1-benzyloxycarbonyl-2-piperidone as an oil.

Workup

  1. customNitrogen was then bubbled for 15 mins
  2. addition16 mL of dimethyl sulfide was added
  3. concentrationconcentrated
  4. customto give a residual oil
  5. temperaturecooled in ice bath
  6. additionwas added
  7. stirringthe mixture was stirred for an additional 15 mins
  8. customSolvent was then removed in vacuo
  9. stirringthe residue was stirred with water and ethyl acetate
  10. customThe organic phase was separated
  11. extractionthe aqueous phase was extracted with ethyl acetate
  12. dry with materialThe combined ethyl acetate extracts were dried over anhydrous magnesium sulfate
  13. customthe solvent was removed in vacuo
  14. customThe resulting residue was purified on silica gel using first 10% ethyl acetate in hexane as solvent

Sources & evidence

ORD record
ord-cd6141147d19402eb5101a1d26a039d6
Source dataset
uspto-grants-1997_05
Patent number
US05629322

Reaction notes

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