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

HRID 2117207Notes

Reaction equation

HRID 2117207 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, G. J.; Morrissey, P. M. 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 stirred for 15 min then warmed to −25° C. Add dropwise iodomethane (405 μL, 6.5 mmol) and let stir for 20 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 soln, brine, dried over MgSO4 and concentrated. The residue is purified by flash chromatography (eluting with 45% ethyl acetate/hexanes) to give 679 mg of title compound.

Workup

  1. stirringlet stir for 20 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 soln
  6. dry with materialbrine, dried over MgSO4
  7. concentrationconcentrated
  8. customThe residue is purified by flash chromatography (eluting with 45% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-148e97211f1c41a3904f906ac4e1cf3c
Source dataset
uspto-grants-2008_10
Patent number
USRE040558E1

Reaction notes

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