2-Piperidone → 1-(4-Methoxybenzyl)piperidin-2-one

HRID 402267Notes

Reaction equation

HRID 402267 reaction equation
[OH-].[K+].[NH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][C:4]1=[O:9].[CH3:10][O:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16]Cl)=[CH:14][CH:13]=1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH3:10][O:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16][N:3]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]2=[O:9])=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 126652-PiperidoneHCID 14797Potassium HydroxideHCID 699934-Methyloxybenzyl chloride

Product 1

HCID 115068011-(4-Methoxybenzyl)piperidin-2-oneYield 52.1%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent2×

Procedure

A suspension of potassium hydroxide (85%, 18.6 g) and tetrabutylammonium bromide (4.88 g) in toluene (250 ml) was refluxed overnight under nitrogen atmosphere using Deenschtark device. The mixture was cooled to 80° C., to which a solution of 2-piperidone (25.0 g) and 4-methoxybenzylchloride (51.3 g) in toluene (50 ml) were added dropwise. After refluxing for 8 hours, the reaction mixture was returned to room temperature and washed with water and saturated brine. The resultant was dried with magnesium sulfate, after which the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane ethyl acetate=1:1) to give 1-(4-methoxybenzyl)piperidin-2-one (28.8 g) as a colorless oily material.

Workup

  1. temperaturewas refluxed overnight under nitrogen atmosphere
  2. additionwere added dropwise
  3. temperatureAfter refluxing for 8 hours
  4. customwas returned to room temperature
  5. washwashed with water and saturated brine
  6. dry with materialThe resultant was dried with magnesium sulfate
  7. distillationafter which the solvent was distilled off under reduced pressure
  8. customthe resulting residue was purified by silica gel column chromatography (hexane ethyl acetate=1:1)

Sources & evidence

ORD record
ord-9d2bd276c5154b68a6d96b3bb8cddab3
Source dataset
uspto-grants-2014_06
Patent number
US08741943B2

Reaction notes

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