Dimethylformamide → 6-Methoxy-1,3,3-trimethylindolin-2-one

HRID 1244026Notes

Reaction equation

HRID 1244026 reaction equation
[H-].[Na+].[CH3:3][N:4]([CH3:7])[CH:5]=[O:6].[CH3:8][O:9][C:10]1[CH:18]=[C:17]2[C:13]([CH2:14][C:15](=O)N2)=C[CH:11]=1.[CH3:20]I>O>[CH3:8][O:9][C:10]1[CH:11]=[C:3]2[C:13]([C:14]([CH3:15])([CH3:20])[C:5](=[O:6])[N:4]2[CH3:7])=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 27937496-Methoxyoxindole

Product 1

HCID 219318586-Methoxy-1,3,3-trimethylindolin-2-oneYield 45%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

In a flame-dried flask under nitrogen, 490 mg of 60% sodium hydride (12.26 mmol) was slurried three times with Hexanes, and the Hexanes were syringed off. Added 6.25 ml of N,N-dimethylformamide, followed by 500 mg of 6-Methoxy-1,3-dihydro-indol-2-one (3.06 mmol) and stirred at room temperature for 5 minutes. Chilled in ice-H2O bath and added 763 μl of methyl iodide (12.26 mmol) dropwise. After 10 minutes, warmed to room temperature and stirred for 1.5 hours. Chilled in ice-H2O bath and added 20 ml of H2O dropwise. Extracted three times with 2:1 EtOAc/toluene. The combined organics were washed with sodium thiosulfate, H2O and brine, dried (MgSO4) and the solvent removed in vacuo to crude red oil. Purified on Biotage Flash 40, eluting with 4:1 Hexanes/EtOAc to give 285 mg of a white solid (45%). 1H NMR (400 MHz, CDCl3) δ 1.31 (6H, s), 3.16 (3H, s), 3.80 (3H, s), 6.41 (1H, d, J=2.28 Hz), 6.53 (1H, m), 7.06 (1H, d, J=8.1 Hz). M/z (APCI+) 206.0 (M+1).

Workup

  1. waitAfter 10 minutes
  2. temperaturewarmed to room temperature
  3. stirringstirred for 1.5 hours
  4. extractionExtracted three times with 2:1 EtOAc/toluene
  5. washThe combined organics were washed with sodium thiosulfate, H2O and brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed in vacuo to crude red oil
  8. customPurified on Biotage Flash 40
  9. washeluting with 4:1 Hexanes/EtOAc

Sources & evidence

ORD record
ord-035bff6f5ecd4f6598968ee6277e19e2
Source dataset
uspto-grants-2006_10
Patent number
US07119207B2

Reaction notes

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