1-Benzyl-4-piperidone → 6-Benzyl-1-oxa-6-azaspiro(2,5)octane

HRID 967767Notes

Reaction equation

HRID 967767 reaction equation
[H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[CH2:9]([N:16]1[CH2:21][CH2:20][C:19](=[O:22])[CH2:18][CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>CS(C)=O>[CH2:9]([N:16]1[CH2:21][CH2:20][C:19]2([CH2:4][O:22]2)[CH2:18][CH2:17]1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 192201-Benzyl-4-piperidoneHCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)

Product 1

HCID 892386-Benzyl-1-oxa-6-azaspiro(2,5)octaneYield 80.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

60% sodium hydride (25.4 g) was added to anhydrous dimethylsulfoxide (400 mL) and the mixture was stirred at room temperature under nitrogen atmosphere. Trimethylsulfoxonium iodide (140 g) was added gradually to the mixture at 20 to 28° C., and the mixture was stirred at room temperature for sixty minutes. An anhydrous dimethylsulfoxide solution (400 mL) of 1-benzyl-4-piperidone (100 g) was added dropwise to the mixture. After stirring the resulting mixture at room temperature for sixty minutes, the reaction mixture was poured into ice-water (2.0 L) gradually with stirring. The mixture was extracted with ethyl acetate, and the organic layer was combined and washed with water (four times) and brine successively. After drying over anhydrous sodium sulfate, the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; ethyl acetate:hexane=1:9 to 1:1) to obtain the titled compound (86.7 g) as an oil.

Workup

  1. stirringthe mixture was stirred at room temperature for sixty minutes
  2. stirringAfter stirring the resulting mixture at room temperature for sixty minutes
  3. stirringwith stirring
  4. extractionThe mixture was extracted with ethyl acetate
  5. washwashed with water (four times) and brine successively
  6. dry with materialAfter drying over anhydrous sodium sulfate
  7. customthe solvent was removed under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (eluent; ethyl acetate:hexane=1:9 to 1:1)

Sources & evidence

ORD record
ord-3b699cadb5f446c283ad7cfa6466d4bb
Source dataset
uspto-grants-2005_10
Patent number
US06956046B2

Reaction notes

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