Hydrogen Peroxide → (3S)-1-[(2,4-dimethoxyphenyl)methyl]-5-oxopyrrolidine-3-carboxylic acid

HRID 83528Notes

Reaction equation

HRID 83528 reaction equation
O.[OH-].[Li+].OO.C([C@H]1COC(=O)N1[C:19]([C@H:21]1[CH2:25][C:24](=[O:26])[N:23]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:29]=2[O:36][CH3:37])[CH2:22]1)=[O:20])C1C=CC=CC=1.S([O-])(O)=[O:39].[Na+]>O.O1CCCC1>[CH3:37][O:36][C:29]1[CH:30]=[C:31]([O:34][CH3:35])[CH:32]=[CH:33][C:28]=1[CH2:27][N:23]1[C:24](=[O:26])[CH2:25][C@H:21]([C:19]([OH:20])=[O:39])[CH2:22]1

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 168937Lithium hydroxide, monohydrateHCID 23665763Sodium BisulfiteHCID 86680364(S)-4-Benzyl-3-[(S)-1-(2,4-dimethoxybenzyl)-5-oxopyrrolidine-3-carbonyl]-2-oxazolidinone

Product 1

HCID 40985411(3S)-1-[(2,4-dimethoxyphenyl)methyl]-5-oxopyrrolidine-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of lithium hydroxide monohydrate (2.0 g) in water (45 ml) was added dropwise 30 wt % aqueous solution of hydrogen peroxide solution (11 ml)) in an ice-sodium chloride cooling bath, and the mixture was stirred for 15 minutes. To this reaction solution was added tetrahydrofuran (36 ml), and then a solution of (S)-4-benzyl-3-[(S)-1-(2,4-dimethoxybenzyl)-5-oxopyrrolidine-3-carbonyl]-2-oxazolidinone (17.2 g) in tetrahydrofuran (144 ml) was added dropwise thereto, and the mixture was stirred for additional 20 minutes. To this reaction solution was slowly added a 10 wt % aqueous solution of sodium hydrogen sulfite (131 ml), and the mixture was stirred at room temperature for 1 hour after removing the bath, and then extracted with ethyl acetate (180 ml). The resulting organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate to chloroform/methanol=9/1). To the resulting product (6.7 g) was added diisopropyl ether (13.4 ml), the mixture was stirred at 70° C., and then cooled to 0° C. with stirring. A solid was collected from this suspension by filtration, dried under reduced pressure to give the titled compound (5.5 g). An analysis of this solid by HPLC analysis condition 1 showed that an isomer with longer retention time was a main product.

Workup

  1. stirringthe mixture was stirred for additional 20 minutes
  2. stirringthe mixture was stirred at room temperature for 1 hour
  3. customafter removing the bath
  4. extractionextracted with ethyl acetate (180 ml)
  5. washThe resulting organic layer was washed with a saturated aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate to chloroform/methanol=9/1)
  9. additionTo the resulting product (6.7 g) was added diisopropyl ether (13.4 ml)
  10. stirringthe mixture was stirred at 70° C.
  11. stirringwith stirring
  12. filtrationA solid was collected from this suspension by filtration
  13. customdried under reduced pressure

Sources & evidence

ORD record
ord-9b4c1d49247a4053bc238f5db94bda08
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Reaction notes

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