Methanol → 1-Benzyl-4,4-dimethoxypiperidin-3-ol

HRID 2372763Notes

Reaction equation

HRID 2372763 reaction equation
[C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-:15].[K+].[C:17](O)(=[O:19])C.C(O)(=O)C.IC1C=CC=CC=1.[CH3:32]O>>[C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][C:11]([O:19][CH3:17])([O:14][CH3:32])[CH:10]([OH:15])[CH2:9]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 4

HCID 887Methanol2×HCID 14797Potassium HydroxideHCID 192201-Benzyl-4-piperidoneHCID 12217721Iodo benzene diacetate

Product 1

HCID 30192741-Benzyl-4,4-dimethoxypiperidin-3-olYield 25.8%

Procedure

1-Phenylmethyl-4-piperidone (18.92g, 100 mmol) in 40ml of methanol was added slowly over a period of 15 minutes to a solution of potassium hydroxide (16.83g, 100 mmol) in I50ml of methanol at 0° C. Iodobenzene diacetate (35.43g, 11O mmol) was then added to the mixture in portions over a period of thirty minutes. The reaction mixture was stirred at room temperature overnight. The mixture was then concentrated under vacuum to remove the excess of methanol and the crude residue was diluted with a mixture cf water (500ml) and dichloromethane (300ml). The dichloromethane layer was separated and the aqueous phase was again extracted with 150ml of dichloromethane. The combined organic layers were dried over sodium sulfate and concentrated under vacuum. The crude residue was dissolved in 100ml of hexane and crystallized. The solid was washed with 30ml of hexane to yield the intermediate I-phenylmethyl-3-hydroxy-4,4-dimethoxypiperidine (3b, 6.48g, 25.8%).

Workup

  1. concentrationThe mixture was then concentrated under vacuum
  2. customto remove the excess of methanol
  3. additionthe crude residue was diluted with a mixture cf water (500ml) and dichloromethane (300ml)
  4. customThe dichloromethane layer was separated
  5. extractionthe aqueous phase was again extracted with 150ml of dichloromethane
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. dissolutionThe crude residue was dissolved in 100ml of hexane
  9. customcrystallized
  10. washThe solid was washed with 30ml of hexane

Sources & evidence

ORD record
ord-f9d2cf4749fc4d57b4a3a257670f8f87
Source dataset
uspto-grants-1992_03
Patent number
US05100903

Reaction notes

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