Sodium hydride → HCID 22235805, compound

HRID 1744076Notes

Reaction equation

HRID 1744076 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][C:13]([O:15][C:16]([CH3:26])([CH3:25])[C:17](=O)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:14].[H-].[Na+]>CN(C=O)C.CCOC(C)=O.CCOCC.Cl>[CH3:25][C:16]1([CH3:26])[O:15][C:13](=[O:14])[C:12]([N:3]2[C:2](=[O:1])[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[C:4]2=[O:11])=[C:17]1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[NH2:3][C:12]1[C:13](=[O:14])[O:15][C:16]([CH3:26])([CH3:25])[C:17]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 2

HCID 24758Sodium hydrideHCID 69152279HCID 69152279, compound

Product 2

HCID 22235805HCID 22235805, compoundHCID 22235995HCID 22235995, compound

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent2×HCID 21584169Diethylether ethylacetateSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. suspension of unpurified 1,1-dimethyl-2-oxo-2-phenylethyl 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetate (4.4 g) in DMF (40 mL) was added a suspension of NaH (1.0 g of 60% dispersion, washed with hexanes) in DMF (10 mL). The mixture was stirred at 0° C. for 2 h, then diluted with EtOAc/ether (1:1) and 1 M HCl. The layers were separated and the organic phase was washed with water and brine, dried over MgSO4 and concentrated. The residue was dissolved in toluene (50 mL), treated with PPTS (100 mg) and heated to reflux with a Dean-Stark trap for 3 h. The solution was cooled, diluted with EtOAc (100 mL) and washed with water and brine. The organic phase was dried over MgSO4 and concentrated. Purification by flash chromatography (30–50% EtOAc/hexanes) provided 2-(5,5-dimethyl-2-oxo-4-phenyl-2,5-dihydro-3-furanyl)-1H-isoindole-1,3(2H)-dione, and 3-amino-5,5-dimethyl-4-phenyl-2(5H)-furanone.

Workup

  1. additionwas added
  2. customThe layers were separated
  3. washthe organic phase was washed with water and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in toluene (50 mL)
  7. additiontreated with PPTS (100 mg)
  8. temperatureheated
  9. temperatureto reflux with a Dean-Stark trap for 3 h
  10. temperatureThe solution was cooled
  11. additiondiluted with EtOAc (100 mL)
  12. washwashed with water and brine
  13. dry with materialThe organic phase was dried over MgSO4
  14. concentrationconcentrated
  15. customPurification by flash chromatography (30–50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-2dc53bf835134c9db30b5255e6510668
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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