Iodine → 1-Benzyl-4-(4-methylphenyl)piperidin-4-ol

HRID 2223706Notes

Reaction equation

HRID 2223706 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1.II.[CH2:11]([N:18]1[CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[NH4+].[Cl-]>CCOCC.CCOC(C)=O>[CH2:11]([N:18]1[CH2:23][CH2:22][C:21]([C:2]2[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=2)([OH:24])[CH2:20][CH2:19]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 807IodineHCID 78054-BromotolueneHCID 192201-Benzyl-4-piperidoneHCID 25517Ammonium Chloride

Product 1

HCID 1986081-Benzyl-4-(4-methylphenyl)piperidin-4-ol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-bromotoluene (1.017 g, 5.94 mmol) in anhydrous Et2O (6 mL), is added dropwise to a mixture of Mg (0.159 g, 6.54 mmol) and a catalytic amount of I2 (0.015 g, 0.26 mmol) in anhydrous Et2O (10 mL). The mixture is stirred at reflux for 5 h under nitrogen. To this cloudy solution is added dropwise at 0° C., a solution of N-benzyl-4-piperidone (1.063 mL, 5.94 mmol) in anhydrous Et2O (6 mL) and the mixture is stirred at reflux for 1.5 h. After cooling, the mixture is poured into sat. NH4Cl (20 mL) and extracted with EtOAc (3×30 mL). The combined organic extracts are washed with brine, dried (MgSO4), filtered and concentrated to provide a crude oil. Flash chromatography (EtOAc/Hex: 3/7) affords the title compound.

Workup

  1. temperatureat reflux for 5 h under nitrogen
  2. additionTo this cloudy solution is added dropwise at 0° C.
  3. temperatureat reflux for 1.5 h
  4. temperatureAfter cooling
  5. extractionextracted with EtOAc (3×30 mL)
  6. washThe combined organic extracts are washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto provide a crude oil

Sources & evidence

ORD record
ord-bd1f8038259b4d7cb355e48acc13a189
Source dataset
uspto-grants-2008_05
Patent number
US07375227B2

Reaction notes

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