Iodine → 1-Benzyl-4-(2-benzyloxyphenyl)-4-piperidinol

HRID 279075Notes

Reaction equation

HRID 279075 reaction equation
[Mg].[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1Br)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.BrCCBr.II.[CH2:23]([N:30]1[CH2:35][CH2:34][C:33](=[O:36])[CH2:32][CH2:31]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:23]([N:30]1[CH2:35][CH2:34][C:33]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[O:9][CH2:2][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)([OH:36])[CH2:32][CH2:31]1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

8

Reactant 6

HCID 807IodineHCID 78391,2-DibromoethaneHCID 192201-Benzyl-4-piperidoneHCID 25517Ammonium ChlorideHCID 5618281-(Benzyloxy)-2-bromobenzene2×HCID 5462224Magnesium

Product 1

HCID 118248891-Benzyl-4-(2-benzyloxyphenyl)-4-piperidinolYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent5×

Conditions

Temperature
65 °C

Procedure

To 30 mL of anhydrous tetrahydrofuran was added 940 mg (39 mmol) of magnesium powder. The one-fifth of a solution obtained by dissolving 10 g (38 mmol) of 2-benzyloxybromobenzene in 30 mL of anhydrous tetrahydrofuran was added. To the resulting mixture were added 0.1 mL of 1,2-dibromoethane and a small amount of iodine, followed by heating to 60 to 70° C. When the reaction started, the remaining portion of the anhydrous tetrahydrofuran solution of 2-benzyloxybromobenzene was added dropwise and the mixture was heated to reflux for further 30 minutes. In the resulting anhydrous tetrahydrofuran solution of Grignard reagent, 7 g (37 mmol) of 1-benzyl-4-piperidone dissolved in 30 mL of anhydrous tetrahydrofuran was added dropwise at room temperature. After heating to reflux for 30 minutes, 10 mL of a saturated aqueous solution of ammonium chloride was added dropwise and the solvent was concentrated under reduced pressure. Water was added to the residue and the mixture was extracted with ether, followed by washing with water and drying. The residue obtained by concentrating the solvent under reduced pressure was purified by chromatography on a silica gel column, whereby 12 g (yield: 87.0%) of 1-benzyl-4-(2-benzyloxyphenyl)-4-piperidinol was obtained.

Workup

  1. customThe one-fifth of a solution obtained
  2. additionwas added
  3. temperaturethe mixture was heated
  4. temperatureto reflux for further 30 minutes
  5. additionwas added dropwise at room temperature
  6. temperatureAfter heating
  7. temperatureto reflux for 30 minutes
  8. concentrationthe solvent was concentrated under reduced pressure
  9. additionWater was added to the residue
  10. extractionthe mixture was extracted with ether
  11. washby washing with water
  12. customdrying
  13. customThe residue obtained
  14. concentrationby concentrating the solvent under reduced pressure
  15. customwas purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-ce5d9405b374480c8ca9f28ca4471c6a
Source dataset
uspto-grants-2002_03
Patent number
US06362203B1

Reaction notes

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