Hydrogen Peroxide → 1-(2,4-Dimethoxybenzyl)-5-oxopyrrolidine-3-carboxylic acid

HRID 83504Notes

Reaction equation

HRID 83504 reaction equation
O.[OH-].[Li+].OO.C([C@@H]1COC(=O)N1[C:19]([CH: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][CH:21]([C:19]([OH:20])=[O:39])[CH2:22]1

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 168937Lithium hydroxide, monohydrateHCID 23665763Sodium BisulfiteHCID 71287868(R)-4-benzyl-3-[1-(2,4-dimethoxybenzyl)-5-oxopyrrolidine-3-carbonyl]-2-oxazolidinone

Product 1

HCID 112544611-(2,4-Dimethoxybenzyl)-5-oxopyrrolidine-3-carboxylic acidYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of lithium hydroxide monohydrate (3.29 g) in water (50 ml) was added dropwise 30 wt % aqueous solution of hydrogen peroxide (17.5 ml) under cooling with an ice-sodium chloride bath, and the mixture was stirred for 15 minutes. To this reaction solution was added tetrahydrofuran (30 ml), and then a solution of the low-polarity component of (R)-4-benzyl-3-[1-(2,4-dimethoxybenzyl)-5-oxopyrrolidine-3-carbonyl]-2-oxazolidinone (26.4 g) in tetrahydrofuran (150 ml) was added dropwise thereto, and the mixture was stirred for additional 1 hour. To this reaction solution was slowly added a solution of sodium hydrogen sulfite (18.7 g) in water (60 ml), and the mixture was warmed to room temperature by removing the bath, and then extracted with ethyl acetate (100 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: chloroform/ethyl acetate=1/1 to 1/2, chloroform/methanol=5/1) to give the titled compound (14.3 g). An analysis of this solid by HPLC analysis condition 2 showed that an isomer with shorter retention time was a main product.

Workup

  1. temperatureunder cooling with an ice-sodium chloride bath
  2. stirringthe mixture was stirred for additional 1 hour
  3. customby removing the bath
  4. extractionextracted with ethyl acetate (100 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: chloroform/ethyl acetate=1/1 to 1/2, chloroform/methanol=5/1)

Sources & evidence

ORD record
ord-fd91731d21a3436a89598306ea511116
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Reaction notes

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