Sodium hydride → 4,5-dichloro-3-hydroxy-3-(2-methoxy-5-methylphenyl)-1,3-dihydro-2H-indol-2-one

HRID 1662612Notes

Reaction equation

HRID 1662612 reaction equation
[H-].[Na+].[Cl:3][C:4]1[C:12]([Cl:13])=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:15])[C:7](=[O:14])[NH:8]2.Br[Mg][C:18]1[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][C:19]=1[O:25][CH3:26].[NH4+].[Cl-]>C1COCC1>[Cl:3][C:4]1[C:12]([Cl:13])=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6]([OH:15])([C:18]1[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][C:19]=1[O:25][CH3:26])[C:7](=[O:14])[NH:8]2

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 51399804,5-Dichloro-1H-indole-2,3-dioneHCID 178489967HCID 178489967, compound

Product 1

HCID 231207064,5-dichloro-3-hydroxy-3-(2-methoxy-5-methylphenyl)-1,3-dihydro-2H-indol-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under nitrogen atmosphere, to a suspension of 0.31 g NaH in THF (40 ml), under ice bath conditions, was added 1.50 g of 4,5-dichloroisatin, which is the compound described in the specifications of U.S. Pat. No. 4,146,718, and the reaction mixture was stirred for 1 hour. Thereafter, a solution of bromo(2-methoxy-5-methylphenyl) magnesium in THF (20 ml) prepared beforehand was added dropwise over 20 minutes. The solution was stirred at the same temperature for 4 hours. Then a saturated aqueous solution of NH4Cl was added, and the reaction mixture was stirred at room temperature for 30 minutes. Liquid separation was performed, the aqueous layer was extracted with EtOAc, the combined organic layer was washed with saturated brine, dried over Na2SO4, then, the drying agent was separated by filtration and the solvent was evaporated under reduced pressure. The obtained residue was washed by stirring in IPE and the solid was collected by filtration to obtain 1.23 g of the title compound (yellow solid).

Workup

  1. additionwas added dropwise over 20 minutes
  2. stirringThe solution was stirred at the same temperature for 4 hours
  3. stirringthe reaction mixture was stirred at room temperature for 30 minutes
  4. customLiquid separation
  5. extractionthe aqueous layer was extracted with EtOAc
  6. washthe combined organic layer was washed with saturated brine
  7. dry with materialdried over Na2SO4
  8. customthe drying agent was separated by filtration
  9. customthe solvent was evaporated under reduced pressure
  10. washThe obtained residue was washed
  11. stirringby stirring in IPE
  12. filtrationthe solid was collected by filtration

Sources & evidence

ORD record
ord-0c4019959040447f8f0e08fc10590132
Source dataset
uspto-grants-2011_10
Patent number
US08030499B2

Reaction notes

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