Iodine → 1-Benzyl-4-hydroxy-4(4-methylphenyl)piperidone

HRID 1493275Notes

Reaction equation

HRID 1493275 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([OH:21])([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.II.[Mg].BrC1C=CC(C)=CC=1.C(N1CCCCC1=[O:46])C1C=CC=CC=1.[Cl-].[NH4+]>BrC1C=CC(C)=CC=1.C(OCC)C>[CH2:1]([N:8]1[CH2:9][CH2:10][C:11]([OH:21])([C:14]2[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=2)[CH2:12][C:13]1=[O:46])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 6

HCID 807IodineHCID 78054-BromotolueneHCID 25517Ammonium ChlorideHCID 1986081-Benzyl-4-(4-methylphenyl)piperidin-4-olHCID 51700761-Benzyl-2-piperidoneHCID 5462224Magnesium

Product 1

HCID 198308531-Benzyl-4-hydroxy-4(4-methylphenyl)piperidone

Reagents, catalysts & solvents 2

HCID 78054-BromotolueneCatalystHCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
20 °C

Procedure

1-Benzyl-4-hydroxy-4-(4-methylphenyl)piperidine may be prepared in the following manner: several drops of p-bromotoluene and a crystal of iodine are added to magnesium turnings (1.7 g) in diethyl ether (25 cc), under a current of argon. The mixture is heated to boiling, then a solution of p-bromotoluene (12.1 g) in diethyl ether (70 cc) is poured in in such a manner as to maintain the reflux. The reaction medium is stirred for 30 minutes at the boiling point of the solvent, then cooled to a temperature of about 20° C. A solution of 1benzylpiperidone (6.7 g) in diethyl ether (60 cc) is added, and stirring is maintained for 15 hours at the same temperature. A saturated solution of ammonium chloride (150 cc) is added to the mixture; the aqueous phase is decanted and the organic phase is extracted with diethyl ether (2 x 150 cc), dried over anhydrous magnesium sulphate, filtered and concentrated to dryness at 40° C. under reduced pressure (20 mm Hg; 2.7 kPa). The residue obtained is purified by flash-chromatography on a silica column, under a current of argon at medium pressure (0.5-1.5 bar) with a mixture of dichloromethane and methanol (95-5 vol) as eluant. 1-Benzyl-4-hydroxy-4(4-methylphenyl)piperidone (5 g) is obtained in the form of an oil, which is used in the crude state in the subsequent syntheses.

Workup

  1. temperatureThe mixture is heated
  2. temperatureto maintain the reflux
  3. stirringstirring
  4. temperatureis maintained for 15 hours at the same temperature
  5. customthe aqueous phase is decanted
  6. extractionthe organic phase is extracted with diethyl ether (2 x 150 cc)
  7. dry with materialdried over anhydrous magnesium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness at 40° C. under reduced pressure (20 mm Hg; 2.7 kPa)
  10. customThe residue obtained
  11. customis purified by flash-chromatography on a silica column
  12. additionunder a current of argon at medium pressure (0.5-1.5 bar) with a mixture of dichloromethane and methanol (95-5 vol) as eluant

Sources & evidence

ORD record
ord-fbf5b23605fe487aa9f5747e6e2741a3
Source dataset
uspto-grants-1991_06
Patent number
US05021420

Reaction notes

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