Methyl iodide → 6-Methoxy-3-methyl-1,3-dihydro-indol-2-one

HRID 892200Notes

Reaction equation

HRID 892200 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][C:8](=[O:12])[NH:9]2)=[CH:5][CH:4]=1.[CH3:13]N(CCN(C)C)C.[Li]CCCC.IC>C1COCC1>[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

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 27937496-MethoxyoxindoleHCID 178418339Butyllithium

Product 1

HCID 222415386-Methoxy-3-methyl-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-25 °C

Procedure

To a cooled solution (−78° C.) of 6-methoxy-1,3-dihydro-indol-2-one (840 mg, 5.2 mmol, See Quallich, Synthesis 1993, 51–53) in THF (20 mL) is added dropwise TMEDA (1.57 mL, 10.4 mL) followed by dropwise addition of 2.5M n-BuLi (4.16 mL, 10.4 mmol). The mixture is allowed to stir for 15 min then warmed to −25° C. Iodomethane (405 μL, 6.5 mmol) is added dropwise and stirred for 20 min. The reaction is quenched with sat NH4Cl soln, warmed to room temp and diluted with EtOAc. Washed organic layer with sat NH4Cl soln, brine, dried over MgSO4 and concentrated. The residue is purified by flash chromatography (silica, 45% ethyl acetate in hexanes) to give the title compound. MS (ESI) 178 (M+H)+.

Workup

  1. stirringstirred for 20 min
  2. customThe reaction is quenched with sat NH4Cl soln
  3. temperaturewarmed to room temp
  4. additiondiluted with EtOAc
  5. dry with materialWashed organic layer with sat NH4Cl soln, brine, dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue is purified by flash chromatography (silica, 45% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-6ba04cfbd46848469ec248f0df1d7b56
Source dataset
uspto-grants-2006_02
Patent number
US07005440B1

Reaction notes

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