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

HRID 1810776Notes

Reaction equation

HRID 1810776 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-79bcaf0de24f418abf078a5825988026
Source dataset
uspto-grants-2013_01
Patent number
US08362058B2

Reaction notes

Loading…