5-(3,5-Dimethylisoxazol-4-yl)indoline-2,3-dione → 5-(3,5-Dimethylisoxazol-4-yl)-3-hydroxy-3-phenylindolin-2-one

HRID 1052955Notes

Reaction equation

HRID 1052955 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][C:11](=[O:16])[C:10]3=[O:17])=[C:5]([CH3:18])[O:4][N:3]=1.[C:19]1([Mg]Br)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C1COCC1>[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][C:11](=[O:16])[C:10]3([OH:17])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:5]([CH3:18])[O:4][N:3]=1

Participants

4

Reactant 2

HCID 1175999855-(3,5-Dimethylisoxazol-4-yl)indoline-2,3-dioneHCID 178418255HCID 178418255, compound

Product 1

HCID 862961015-(3,5-Dimethylisoxazol-4-yl)-3-hydroxy-3-phenylindolin-2-oneYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

5-(3,5-Dimethylisoxazol-4-yl)indoline-2,3-dione (24.2 g, 0.1 mol) was dissolved in anhydrous THF (400 mL) and cooled to 0° C. followed by dropwise addition of a 2.0 M solution of PhMgBr in THF (110 mL, 220.0 mmol). The ice-bath was removed, and the reaction was stirred under N2 for 30 min at which point TLC analysis indicated complete consumption of the starting material. The reaction mixture was quenched with saturated aqueous NH4Cl (100 mL), and extracted with EtOAc (3×100 ml). The combined organic layers were washed with saturated aqueous NaHCO3 (100 ml), brine (100 ml), dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was evacuated under high vacuum to give the crude alcohol (30 g, 94%). 1H NMR (400 MHz, DMSO-d6): δ 10.50 (s, 1H), 7.22-7.32 (m, 6H), 7.09 (d, J=1.2 Hz, 1H), 6.99 (d, J=8.0 Hz, 1H), 6.71 (brs, 1H), 2.32 (s, 3H), 2.15 (s, 3H) MS (ESI) m/e [M+1]+ 321.

Workup

  1. customThe ice-bath was removed
  2. customconsumption of the starting material
  3. customThe reaction mixture was quenched with saturated aqueous NH4Cl (100 mL)
  4. extractionextracted with EtOAc (3×100 ml)
  5. washThe combined organic layers were washed with saturated aqueous NaHCO3 (100 ml), brine (100 ml)
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was evacuated under high vacuum

Sources & evidence

ORD record
ord-b1b83a20bff14fbfb200bc582130e9f5
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

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