Ozone → (4R)-4-Benzyloxymethyl-4-(2-hydroxyethyl)-1-[(1R)-1-phenylethyl]pyrrolidin-2-one

HRID 1917314Notes

Reaction equation

HRID 1917314 reaction equation
[CH2:1]([C@:4]1([CH2:18][O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:8][N:7]([C@@H:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH3:10])[C:6](=[O:17])[CH2:5]1)[CH:2]=C.[O:27]=[O+][O-].[BH4-].[Na+].[Cl-].[NH4+]>ClCCl.O.C(OCC)(=O)C.CO>[CH2:20]([O:19][CH2:18][C@@:4]1([CH2:1][CH2:2][OH:27])[CH2:8][N:7]([C@@H:9]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH3:10])[C:6](=[O:17])[CH2:5]1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

9

Reactant 4

HCID 24823Ozone2×HCID 25517Ammonium ChlorideHCID 4311764Sodium borohydride2×HCID 67490774(4R)-4-Allyl-4-benzyloxymethyl-1-[(1R)-1-phenylethyl]pyrrolidin-2-one

Product 1

HCID 67490855(4R)-4-Benzyloxymethyl-4-(2-hydroxyethyl)-1-[(1R)-1-phenylethyl]pyrrolidin-2-oneYield 79%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (4R)-4-allyl-4-benzyloxymethyl-1-[(1R)-1-phenylethyl]pyrrolidin-2-one (4.00 g, 11.45 mmol) in dichloromethane (100 mL) was bubbled with ozone gas at −70° C. and stirred at the same temperature for 15 minutes. Ozone bubbling was stopped when the reaction solution was turned dark blue, and then the reaction solution was bubbled with nitrogen gas until the solution turned colorless. Sodium borohydride (434 mg, 11.45 mmol) and methanol (40 mL) were added at the same temperature, and the mixture was heated to room temperature over three hours. Sodium borohydride (325 mg, 8.58 mmol) was added, and the mixture was stirred at room temperature for further 24 hours. A saturated ammonium chloride solution was added, and the mixture was stirred for 10 minutes. Then, the reaction solution was poured into a mixture of ethyl acetate (200 mL) and water (200 mL), followed by extraction with ethyl acetate (500 mL). The organic layer was washed with brine (200 mL), and then dried over anhydrous sodium sulfate and filtered. The filtrate was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:2→1:9→0:1) to give 3.22 g (79%) of the title compound as a colorless viscous oil.

Workup

  1. customthe reaction solution was bubbled with nitrogen gas until the solution
  2. stirringthe mixture was stirred at room temperature for further 24 hours
  3. stirringthe mixture was stirred for 10 minutes
  4. extractionfollowed by extraction with ethyl acetate (500 mL)
  5. washThe organic layer was washed with brine (200 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was then concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:2→1:9→0:1)

Sources & evidence

ORD record
ord-d20b2dfa941c432fa787328c2a428485
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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