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

HRID 1004927Notes

Reaction equation

HRID 1004927 reaction equation
[BH4-].[Na+].[CH2:3]([N:10]1[CH2:15][CH:14]=[C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([Br:22])[CH:17]=2)[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.B(F)(F)F.CC[O:29]CC.[OH-].[K+].OO.B(O)(O)O>C(COC)OC.O>[CH2:3]([N:10]1[CH2:11][CH2:12][CH:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([Br:22])[CH:17]=2)[CH:14]([OH:29])[CH2:15]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

9

Reactant 6

HCID 784Hydrogen PeroxideHCID 7628Boric AcidHCID 8000Boron trifluoride etherateHCID 14797Potassium HydroxideHCID 4311764Sodium borohydrideHCID 221269161-Benzyl-4-(3-bromophenyl)-1,2,3,6-tetrahydro-pyridine

Product 1

HCID 22127354(3RS,4RS)-1-benzyl-4-(3-bromophenyl)-piperidin-3-olYield 63%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent2×

Procedure

3.15 g (83.3 mmol) of sodium borohydride were added portionwise at room temperature to a suspension of 9.5 g (28.9 mmol) of 1-benzyl-4-(3-bromophenyl)-1,2,3,6-tetrahydro-pyridine in 65 ml of absolute dimethoxyethane (DME). Thereafter, a solution of 17.7 ml (20.0 g 140.9 mmol) of boron trifluoride etherate in 11 ml of DME was added dropwise at 15-20° C. and the mixture was stirred at room temperature for 2 hours. Subsequently, a solution of 18.3 g (326 mmol) of potassium hydroxide in 100 ml of water was added dropwise within 30 minutes at 20-25° C. Finally, 55 ml of 30% hydrogen peroxide solution were added dropwise within 30 minutes at 20-25° C. The mixture was stirred at room temperature for 30 minutes and heated to reflux for 3 hours. After cooling the reaction mixture the separated boric acid was filtered off. Subsequently, the filtrate was partitioned between methylene chloride and water, the organic phase was dried over magnesium sulphate and the solvent was removed under reduced pressure. The crude product was purified by chromatography on silica gel with a 1:1 mixture of ethyl acetate and methylene chloride as the eluent. There were obtained 6.3 g (63% of theory) of (3RS,4RS)-1-benzyl-4-(3-bromophenyl)-piperidin-3-ol as a colourless oil. MS: 345, 347 (M)+.

Workup

  1. stirringThe mixture was stirred at room temperature for 30 minutes
  2. temperatureheated
  3. temperatureto reflux for 3 hours
  4. filtrationwas filtered off
  5. customSubsequently, the filtrate was partitioned between methylene chloride and water
  6. dry with materialthe organic phase was dried over magnesium sulphate
  7. customthe solvent was removed under reduced pressure
  8. customThe crude product was purified by chromatography on silica gel with a 1:1 mixture of ethyl acetate and methylene chloride as the eluent

Sources & evidence

ORD record
ord-ecfbc234e02c45e882ae1426cb2577bb
Source dataset
uspto-grants-2000_04
Patent number
US06051712

Reaction notes

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