Hydrogen Peroxide → trans-1-Benzyl-4-(4-methoxyphenyl)piperidin-3-ol

HRID 1507181Notes

Reaction equation

HRID 1507181 reaction equation
[BH4-].[Na+].B(F)(F)F.CC[O:9]CC.[CH2:12]([N:19]1[CH2:24][CH:23]=[C:22]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[CH2:21][CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[OH-].[Na+].OO>C1COCC1.[Cl-].[NH4+].C(O)C>[CH2:12]([N:19]1[CH2:20][CH2:21][C@@H:22]([C:25]2[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)[C@H:23]([OH:9])[CH2:24]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

9

Reactant 5

HCID 784Hydrogen PeroxideHCID 8000Boron trifluoride etherateHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 106364031-Benzyl-4-(4-methoxyphenyl)-1,2,3,6-tetrahydropyridine

Product 1

HCID 118207341trans-1-Benzyl-4-(4-methoxyphenyl)piperidin-3-olYield 69%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

To a suspension of sodium tetrahydroborate (2.7 g, 72 mmol) in THF (200 mL) 0° C. was added dropwise boron trifluoride etherate (8.8 mL, 70 mmol) under a nitrogen atmosphere and the resulting mixture was stirred for 30 minutes. Then was added 1-benzyl-4-(4-methoxyphenyl)-1,2,3,6-tetrahydropyridine (10 g, 36 mmol) (from S. Halazy et al WO 97/28140 (8/7/97)) dissolved in 100 mL of tetrahydrofuran. Stirring was continued at rt for 2 hours. The reaction was then quenched by the dropwise addition of 100 mL water. Next were added sequentially 100 mL ethanol, 100 mL 10% aqueous sodium hydroxide, and hydrogen peroxide (18 mL, 18 mmol) and the temperature was raised to reflux overnight. The reaction mixture was diluted with saturated aqueous ammonium chloride (200 mL), and extracted with ethyl acetate (500 mL). The organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure to give trans-1-benzyl-4-(4-methoxyphenyl)piperidin-3-ol (8.5 g, 24.6 mmol, 69% yield). LCMS (Method K) RT 1.99 min; m/z 298.0 (MH+).

Workup

  1. stirringStirring
  2. waitwas continued at rt for 2 hours
  3. customThe reaction was then quenched by the dropwise addition of 100 mL water
  4. temperaturethe temperature was raised
  5. temperatureto reflux overnight
  6. extractionextracted with ethyl acetate (500 mL)
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-eb304b32cdad48bc8725742cb6cca81c
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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