Hydrogen Peroxide → (3RS,4RS)-1-benzyl-4-(4-bromo-phenyl)-piperidin-3-ol

HRID 1004982Notes

Reaction equation

HRID 1004982 reaction equation
FC1C=CC(C2CCNCC2[O:14]CC2C(O)=CC3C(=CC=CC=3)C=2)=CC=1.[BH4-].[Na+].[CH2:29]([N:36]1[CH2:41][CH:40]=[C:39]([C:42]2[CH:47]=[CH:46][C:45]([Br:48])=[CH:44][CH:43]=2)[CH2:38][CH2:37]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.B(F)(F)F.CCOCC.[OH-].[K+].OO>C(COC)OC.O.C(Cl)Cl>[CH2:29]([N:36]1[CH2:37][CH2:38][CH:39]([C:42]2[CH:43]=[CH:44][C:45]([Br:48])=[CH:46][CH:47]=2)[CH:40]([OH:14])[CH2:41]1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

10

Reactant 6

HCID 784Hydrogen PeroxideHCID 8000Boron trifluoride etherateHCID 14797Potassium HydroxideHCID 4311764Sodium borohydrideHCID 112443314-(4-Bromophenyl)-1,2,3,6-tetrahydro-1-(phenylmethyl)pyridineHCID 22126512(3RS,4RS)-4-(4-Fluorophenyl)-3-(3-hydroxy-naphthalen-2-ylmethoxy)-piperidine

Product 1

HCID 22128081(3RS,4RS)-1-benzyl-4-(4-bromo-phenyl)-piperidin-3-olYield 456%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

1 6.9 g of sodium borohydride were added to a solution of 51.1 g (0.156 mol) of 1-benzyl-4-(4-bromo-phenyl)-1,2,3,6-tetrahydro-pyridine in 350 ml of dimethoxyethane and the reaction mixture was stirred at room temperature for 15 minutes. Thereafter, 95.2 ml of boron trifluoride etherate were added dropwise at 25-30° C. during 30 minutes, the reaction mixture was subsequently stirred at room temperature for 2 hours. Thereafter, firstly a solution of 98.4 g of potassium hydroxide in 530 ml of water was slowly added dropwise and thereafter within 15 minutes 80.7 ml of a 30% hydrogen peroxide solution were added. Subsequently, the mixture was boiled under reflux for 2 hours. For the working-up, the cooled reaction mixture was filtered over Dicalit and this was rinsed with methylene chloride. The solution obtained was treated with 700 ml of methylene chloride, the organic phase was separated and then the aqueous phase was back-extracted with 300 ml of methylene chloride. The combined organic phases were washed twice with 200 ml of water each time, dried over magnesium sulphate and evaporated under reduced pressure. Crystallization of the crude product from acetone yielded 31 g (57% of theory) of (3RS,4RS)-1-benzyl-4-(4-bromo-phenyl)-piperidin-3-ol as colourless crystals; m.p.: 125-129° C.

Workup

  1. stirringthe reaction mixture was subsequently stirred at room temperature for 2 hours
  2. temperatureunder reflux for 2 hours
  3. customthe cooled reaction mixture
  4. filtrationwas filtered over Dicalit
  5. washthis was rinsed with methylene chloride
  6. customThe solution obtained
  7. customthe organic phase was separated
  8. extractionthe aqueous phase was back-extracted with 300 ml of methylene chloride
  9. washThe combined organic phases were washed twice with 200 ml of water each time
  10. dry with materialdried over magnesium sulphate
  11. customevaporated under reduced pressure
  12. customCrystallization of the crude product from acetone

Sources & evidence

ORD record
ord-da49656d7ed04c40b176e7eb4d69d83c
Source dataset
uspto-grants-2000_04
Patent number
US06051712

Reaction notes

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