6-Aminophthalide → 3-(6-Amino-3H-isobenzofuran-1-ylidene)-5-chloro-1,3-dihydro-indol-2-one

HRID 1829004Notes

Reaction equation

HRID 1829004 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.C[Si](C)(C)N[Si](C)(C)C.[Na].[NH2:22][C:23]1[CH:32]=[C:31]2[C:26]([CH2:27][O:28][C:29]2=O)=[CH:25][CH:24]=1>C(COC)OC>[NH2:22][C:23]1[CH:32]=[C:31]2[C:26]([CH2:27][O:28][C:29]2=[C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([Cl:1])[CH:3]=3)[NH:7][C:6]2=[O:11])=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 936316-AminophthalideHCID 1528015-ChlorooxindoleHCID 45051731Sodium hexamethyidisilazane

Product 1

HCID 684618673-(6-Amino-3H-isobenzofuran-1-ylidene)-5-chloro-1,3-dihydro-indol-2-oneYield 39%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

To a solution of 5-chlorooxindole (0.629 g, 3.78 mmol) in 10.0 mL monoglyme was added 7.51 mL sodium hexamethyldisilazane (1.0 M in THF) over 3 min. After stirring at room temperature for 8 min, a slurry of 6-aminophthalide (0.561 g, 3.78 mmol) in 4.0 mL of monoglyme was added in one portion. The mixture was stirred for 40 min and then quenched into 100 mL of 4% aqueous HCl solution. The yellow solid was filtered and then partitioned between EtOAc and saturated NaHCO3 (heated to dissolve the solid). The organic phase was washed with H2O, brine and then dried with Na2SO4. The solvent was removed in vacuo and the residue was triturated with MeOH to give the title compound (439 mg, 39%) as a yellow solid.

Workup

  1. stirringThe mixture was stirred for 40 min
  2. customquenched into 100 mL of 4% aqueous HCl solution
  3. filtrationThe yellow solid was filtered
  4. custompartitioned between EtOAc and saturated NaHCO3 (
  5. temperatureheated
  6. dissolutionto dissolve the solid)
  7. washThe organic phase was washed with H2O, brine
  8. dry with materialdried with Na2SO4
  9. customThe solvent was removed in vacuo
  10. customthe residue was triturated with MeOH

Sources & evidence

ORD record
ord-22e72dd927b740faba5e730eba88e896
Source dataset
uspto-grants-2006_06
Patent number
US07060844B2

Reaction notes

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