Methyl iodide → 6-Methoxy-3,3-dimethylindolin-2-one

HRID 988255Notes

Reaction equation

HRID 988255 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]([CH3:13])[C:8](=[O:12])[NH:9]2)=[CH:5][CH:4]=1.[CH3:14]N(CCN(C)C)C.[Li]CCCC.IC>C1COCC1>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH3:14])([CH3:13])[C:8](=[O:12])[NH:9]2)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 222415386-Methoxy-3-methyl-1,3-dihydro-indol-2-oneHCID 178418339Butyllithium

Product 1

HCID 222416036-Methoxy-3,3-dimethylindolin-2-oneYield 82.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-25 °C

Procedure

To a cooled solution (−78° C.) of 6-methoxy-3-methyl-1,3-dihydro-indol-2-one (679 mg, 3.83 mmol) in THF (13 mL) is added TMEDA (1.16 mL, 7.66 mmol) followed by dropwise addition of 2.5M n-BuLi (3.06 mL, 7.66 mmol). The mixture is stirred for 15 min then warmed to −25° C. Add dropwise iodomethane (275 μL, 4.40 mmol) and let stir for 30 min. The reaction is quenched with sat NH4Cl soln, warmed to room temp and diluted with EtOAc. The organic layer is washed with sat NH4Cl soin, brine, dried over MgSO4 and concentrated. The residue is purified by flash chromatography (eluting with 35% ethyl acetate/hexanes) to give 601 mg of title compound as a white crystalline solid. MS (ESI) 192 (M+H)+.

Workup

  1. stirringlet stir for 30 min
  2. customThe reaction is quenched with sat NH4Cl soln
  3. temperaturewarmed to room temp
  4. additiondiluted with EtOAc
  5. washThe organic layer is washed with sat NH4Cl soin
  6. dry with materialbrine, dried over MgSO4
  7. concentrationconcentrated
  8. customThe residue is purified by flash chromatography (eluting with 35% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-7cc7a28e9b074eac875ab85a67cea185
Source dataset
uspto-grants-2003_10
Patent number
US06635655B1

Reaction notes

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