Hydrogen Peroxide → 5-(2,4-Dimethoxybenzyl)-4-oxo-5-azaspiro[2.4]heptane-7-carboxylic Acid

HRID 83586Notes

Reaction equation

HRID 83586 reaction equation
O.[OH-].[Li+].OO.C([C@@H]1COC(=O)N1[C:19]([CH:21]1[C:25]2([CH2:27][CH2:26]2)[C:24](=[O:28])[N:23]([CH2:29][C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][C:31]=2[O:38][CH3:39])[CH2:22]1)=[O:20])C1C=CC=CC=1.S([O-])(O)=[O:41].[Na+]>O.O1CCCC1>[CH3:39][O:38][C:31]1[CH:32]=[C:33]([O:36][CH3:37])[CH:34]=[CH:35][C:30]=1[CH2:29][N:23]1[CH2:22][CH:21]([C:19]([OH:20])=[O:41])[C:25]2([CH2:26][CH2:27]2)[C:24]1=[O:28]

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 168937Lithium hydroxide, monohydrateHCID 23665763Sodium BisulfiteHCID 86680394HCID 86680394, compound

Product 1

HCID 866803935-(2,4-Dimethoxybenzyl)-4-oxo-5-azaspiro[2.4]heptane-7-carboxylic AcidYield 40.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of lithium hydroxide monohydrate (142 mg) in water (5 ml) was added 30 wt % aqueous solution of hydrogen peroxide (0.8 ml) at −5° C., and the mixture was stirred for 15 minutes. To this reaction mixture were sequentially added tetrahydrofuran (5 ml) and a solution of an optically active compound of 7-((R)-4-benzyl-2-oxooxazolidine-3-carbonyl)-5-(2,4-dimethoxybenzyl)-5-azaspiro[2.4]heptan-4-one (1.39 g) in tetrahydrofuran (10 ml), and the mixture was stirred for additional 1 hour. To this reaction mixture was added a solution of sodium hydrogen sulfite (815 mg) in water (5 ml), and the mixture was stirred at room temperature for 1 hour, and then extracted with ethyl acetate. This 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 only). To the resulting solid was added diisopropyl ether/ethyl acetate/n-hexane (10/1/5, 10 ml), and the mixture was stirred. A solid was collected from this suspension by filtration, and dried under reduced pressure to give the titled compound (372 mg).

Workup

  1. stirringthe mixture was stirred at room temperature for 1 hour
  2. extractionextracted with ethyl acetate
  3. washThis organic layer was washed with a saturated aqueous solution of sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (eluent
  7. additionTo the resulting solid was added diisopropyl ether/ethyl acetate/n-hexane (10/1/5, 10 ml)
  8. stirringthe mixture was stirred
  9. filtrationA solid was collected from this suspension by filtration
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-438a48972acb489f88852c7230a08c4b
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Reaction notes

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