Ozone → (4R)-4-(2-Hydroxyethyl)-4-methoxymethyl-1-[(1R)-1-phenylethyl]pyrrolidin-2-one

HRID 1917321Notes

Reaction equation

HRID 1917321 reaction equation
[CH2:1]([C@:4]1([CH2:18][O:19][CH3:20])[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:21]=[O+][O-].[BH4-].[Na+].[Cl-].[NH4+]>CO.O.C(OCC)(=O)C.ClCCl>[OH:21][CH2:2][CH2:1][C@:4]1([CH2:18][O:19][CH3:20])[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

Participants

9

Reactant 4

HCID 24823Ozone2×HCID 25517Ammonium ChlorideHCID 4311764Sodium borohydride3×HCID 67490961(4R)-4-Allyl-4-methoxymethyl-1-[(1R)-1-phenylethyl]pyrrolidin-2-one

Product 1

HCID 67491006(4R)-4-(2-Hydroxyethyl)-4-methoxymethyl-1-[(1R)-1-phenylethyl]pyrrolidin-2-oneYield 86%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (4R)-4-allyl-4-methoxymethyl-1-[(1R)-1-phenylethyl]pyrrolidin-2-one (3.28 g, 12.0 mmol) in methanol (20 mL)-dichloromethane (20 mL) was bubbled with ozone gas at −70° C. and stirred at the same temperature for 30 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 (454 mg, 12.0 mmol) was added at the same temperature, and the mixture was heated to room temperature over two hours. After heating, sodium borohydride (227 mg, 6.0 mmol) was added and the mixture was stirred for 24 hours. Then, sodium borohydride (113 mg, 3.0 mmol) was further added and the mixture was stirred for 0.5 hour. A saturated ammonium chloride solution (10 mL) was added, and the mixture was stirred for 10 minutes. Then, the reaction solution was poured into a mixture of ethyl acetate (50 mL) and water (50 mL), followed by extraction with ethyl acetate (200 mL). The organic layer was washed with brine (50 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 (ethyl acetate:methanol=10:0→10:1) to give 2.85 g (86%) of the title compound as a colorless viscous oil.

Workup

  1. customthe reaction solution was bubbled with nitrogen gas until the solution
  2. temperatureAfter heating
  3. stirringthe mixture was stirred for 24 hours
  4. stirringthe mixture was stirred for 0.5 hour
  5. stirringthe mixture was stirred for 10 minutes
  6. extractionfollowed by extraction with ethyl acetate (200 mL)
  7. washThe organic layer was washed with brine (50 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was then concentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:0→10:1)

Sources & evidence

ORD record
ord-61d5d5057dbf491cb3ccea48af78df96
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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