Triethylamine → 5-(3,5-Dimethylisoxazol-4-yl)indoline-2,3-dione

HRID 513249Notes

Reaction equation

HRID 513249 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[O:12].C[N:14]1[CH2:18][C:17](B(O)O)=[C:16]([CH3:22])[O:15]1.[CH2:23](N(CC)CC)C>O.CC(O)C>[CH3:23][C:18]1[C:17]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][C:6](=[O:11])[C:5]3=[O:12])=[C:16]([CH3:22])[O:15][N:14]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 886955-IodoisatinHCID 671525732,5-Dimethylisoxazole-4-boronic acid

Product 1

HCID 1175999855-(3,5-Dimethylisoxazol-4-yl)indoline-2,3-dione

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

5-iodo-1H-indole-2,3-dione (24.0 g, 83.5 mmol) and 2,5-dimethylisoxazole-4-boronic acid (16.0 g, 111.3 mmol) are dissolved in a mixture of water (400 mL) and 2-propanol (800 mL). Triethylamine (36.0 mL, 253.3 mmol) is added followed by 1,1-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (1.0 g, 1.4 mmol). The mixture is purged with argon and then heated at reflux for 5 hours. The solvent is removed in vacuo and the residue partitioned between water and dichloromethane. The organic phase is dried over magnesium sulfate. And the volatiles removed in vacuo. The residue is purified by column chromatography on silica gel using a cyclohexane/ethyl acetate gradient. This afforded the desired product.

Workup

  1. customThe mixture is purged with argon
  2. temperatureheated
  3. temperatureat reflux for 5 hours
  4. customThe solvent is removed in vacuo
  5. customthe residue partitioned between water and dichloromethane
  6. dry with materialThe organic phase is dried over magnesium sulfate
  7. customAnd the volatiles removed in vacuo
  8. customThe residue is purified by column chromatography on silica gel using a cyclohexane/ethyl acetate gradient

Sources & evidence

ORD record
ord-505b41cbca5f466da02ee2411c104880
Source dataset
uspto-grants-2015_08
Patent number
US09102684B2

Reaction notes

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