Hydrogen Peroxide → (3S,4S)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol

HRID 650726Notes

Reaction equation

HRID 650726 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH2:16][CH2:17][N:18]([C@@H:21]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH3:22])[CH2:19][CH:20]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Na].[BH4-].[OH-:31].[Na+].OO.[Na+].[Cl-]>C(OCC)(=O)C.C(COC)OC>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]2[CH2:16][CH2:17][N:18]([C@@H:21]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH3:22])[CH2:19][C@H:20]2[OH:31])=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 784Hydrogen PeroxideHCID 5234Sodium ChlorideHCID 14798Sodium HydroxideHCID 99073724-[4-(Benzyloxy)phenyl]-1-[(1R)-1-phenylethyl]-1,2,3,6-tetrahydropyridineHCID 131720715CID 131720715

Product 1

HCID 11176698(3S,4S)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

The reaction flask was charged under argon with 60 g (162 mmol) of (R)-4-(4-benzyloxy-phenyl)-1-(1-phenyl-ethyl)-1,2,3,6-tetrahydro-pyridine and 600 mL of dimethoxyethane. After addition of 9.2 g (243 mmol) of sodium-borohydride the mixture was cooled to 0° C. under stirring. Then 45.9 g (323 mmol) of borontrifluoride-diethyletherate was added during 40 min, wherein the temperature was kept at 0-5° C. The reaction mixture was stirred at 5° C. for additional 2 h and then at room temperature for 165 min. After cooling to 0° C., 350 mL of 4 N NaOH was added during 1 h, wherein the temperature was kept at 5-10° C. Then 60 mL of 30% H2O2 was added at 20° C. during 1 h. After additional stirring for 20 min the mixture was heated to 45° C., which caused the temperature to raise temporarily to 55° C. After cooling, the temperature was kept at 45° C. for a total of 3 h. After stirring overnight at room temperature the reaction mixture was poured into a mixture of 1 L half-saturated NaCl solution and 800 mL of ethyl acetate. After extraction with ethyl acetate the organic phases were washed with water and dried over Na2SO4. After concentration, 67.4 g of the diastereomeric mixture of (3R,4R)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol and (3S,4S)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol were obtained in a ratio of 3:1.

Workup

  1. customwas kept at 0-5° C
  2. stirringThe reaction mixture was stirred at 5° C. for additional 2 h
  3. temperatureAfter cooling to 0° C.
  4. customwas kept at 5-10° C
  5. stirringAfter additional stirring for 20 min the mixture
  6. temperaturewas heated to 45° C.
  7. temperatureto raise temporarily to 55° C
  8. temperatureAfter cooling
  9. customwas kept at 45° C. for a total of 3 h
  10. stirringAfter stirring overnight at room temperature the reaction mixture
  11. extractionAfter extraction with ethyl acetate the organic phases
  12. washwere washed with water
  13. dry with materialdried over Na2SO4
  14. concentrationAfter concentration, 67.4 g of the diastereomeric mixture of (3R,4R)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol

Sources & evidence

ORD record
ord-2688c645ff15415aa085ae8f482ab99a
Source dataset
uspto-grants-2001_08
Patent number
US06274735B1

Reaction notes

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