Methyl iodide → N-Methyl-5-benzyloxyindole

HRID 2235862Notes

Reaction equation

HRID 2235862 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:21]>CN(C=O)C.O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH3:21])[CH:13]=[CH:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 146245-BenzyloxyindoleHCID 24758Sodium hydride

Product 1

HCID 259196N-Methyl-5-benzyloxyindoleYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 6228DimethylformamideSolvent

Procedure

5-(Benzyloxy)-1H-indole (300 mg, 1.34 mmol) was dissolved in anhydrous DMF under an atmosphere of argon and cooled in a water bath. Sodium hydride (60% dispersion in mineral oil, 64.5 mg, 1.61 mmol) was added, and the mixture was stirred for 30 min. Iodomethane (247.9 mg, 1.75 mmol) was added and stirring was continued for 12 h at 40° C. The mixture was cooled to rt, 10 drops of water were added, and the reaction mixture was concentrated under reduced pressure. The residue was taken up in water and was extracted with EtOAc (2×). Purification by silica gel flash chromatography (EtOAc/hexane (v/v)=1:7) gave 254 mg (80%) of the title compound as a white crystalline solid. 1H NMR (400 MHz, CDCl3): δ 3.78 (s, 3H), 5.11 (s, 2H), 6.40 (br, 1H), 6.94 (d, 1H), 7.00 (s, 1H), 7.17 (s, 1H), 7.20-7.48 (m, 6H).

Workup

  1. temperaturecooled in a water bath
  2. stirringstirring
  3. waitwas continued for 12 h at 40° C
  4. concentrationthe reaction mixture was concentrated under reduced pressure
  5. extractionwas extracted with EtOAc (2×)
  6. customPurification by silica gel flash chromatography (EtOAc/hexane (v/v)=1:7)

Sources & evidence

ORD record
ord-4b07e944f83a44c6acbd0898c64da193
Source dataset
uspto-grants-2010_05
Patent number
US07714004B2

Reaction notes

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