p-Xylyl bromide → 4-Hydroxy-4-(4-methyl-benzyl)-piperidin-1-carboxylic acid ethylester

HRID 1419904Notes

Reaction equation

HRID 1419904 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][C:9](=[O:12])[CH2:8][CH2:7]1)=[O:5])[CH3:2].[CH3:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18]Br)=[CH:16][CH:15]=1>C(OCC)C.Cl.[NH4+].O>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][C:9]([OH:12])([CH2:13][C:14]2[CH:21]=[CH:20][C:17]([CH3:18])=[CH:16][CH:15]=2)[CH2:10][CH2:11]1)=[O:5])[CH3:2]

Participants

6

Reactant 2

HCID 7721p-Xylyl bromideHCID 34767Ethyl 4-oxo-1-piperidinecarboxylate

Product 1

HCID 537913684-Hydroxy-4-(4-methyl-benzyl)-piperidin-1-carboxylic acid ethylesterYield 99%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent3×HCID 21905121Ammonium hydrochlorideSolvent

Procedure

A solution of 1-ethoxycarbonyl-4-piperidone (39 ml, 0.26 mol) in diethylether (150 ml) was added dropwise at room temperature to a solution prepared from 4-methyl-benzylbromide (237 g, 1.28 mol) and Mg (31.2 g, 1.28 mol) in diethylether (300 ml). Room temperature was maintained for 45 min with stirring and the mixture was then refluxed for 5 h. It was cooled to 0° C., diluted with diethylether (700 ml) and hydrolyzed with saturated ammoniumhydrochloride solution (200 ml) and water (350 ml). Insoluble material was removed by filtration over Celite", the residue washed twice with diethylether (2×500 ml) and the organic phase was separated. The water layer was extracted with diethylether, the organic phases were pooled and dried with MgSO4 and the solvent evaporated. The residue was chromatographed over silica gel (hexane-ethyl acetate, 2:1) to give 4-hydroxy-4-(4-methyl-benzyl)-piperidin-1-carboxylic acid ethylester (70.5 g, 99%) as a yellowish oil, MS: m/e=278 (M+H+).

Workup

  1. temperaturethe mixture was then refluxed for 5 h
  2. temperatureIt was cooled to 0° C.
  3. customInsoluble material was removed by filtration over Celite"
  4. washthe residue washed twice with diethylether (2×500 ml)
  5. customthe organic phase was separated
  6. extractionThe water layer was extracted with diethylether
  7. dry with materialdried with MgSO4
  8. customthe solvent evaporated
  9. customThe residue was chromatographed over silica gel (hexane-ethyl acetate, 2:1)

Sources & evidence

ORD record
ord-641f9e16f29540089b430427fc7f08d5
Source dataset
uspto-grants-1999_03
Patent number
US05889026

Reaction notes

Loading…