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

HRID 1507214Notes

Reaction equation

HRID 1507214 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) at 0° C. under a nitrogen atmosphere was added dropwise boron trifluoride etherate (8.8 mL, 70 mmol) and the resulting mixture was stirred for 30 minutes. Then 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 was added. The mixture was allowed to warm to rt and stirred for 2 h. The reaction was then quenched by the dropwise addition of 100 mL of water. Next were added sequentially 100 mL of ethanol, 100 mL of a 10% aqueous sodium hydroxide solution, and 30% hydrogen peroxide (18 mL, 180 mmol) and the mixture was stirred at reflux temperature overnight. The reaction mixture was then allowed to cool, 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 (±)-rel-(3S,4S)-1-benzyl-4-(4-methoxyphenyl)piperidin-3-ol (8.5 g, 24.6 mmol, 69% yield) which was used without further purification. LCMS (Method K) RT 1.99 min; m/z 298.0 (M+H+).

Workup

  1. additionwas added
  2. stirringstirred for 2 h
  3. customThe reaction was then quenched by the dropwise addition of 100 mL of water
  4. stirringthe mixture was stirred
  5. temperatureat reflux temperature overnight
  6. temperatureto cool
  7. extractionextracted with ethyl acetate (500 mL)
  8. dry with materialThe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-5bb665c8cc8943adbdb638210ddfbbc5
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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