Methyl iodide → 5-methoxy-1-methyl-1H-indole-3-carbaldehyde

HRID 430928

Reaction equation

HRID 430928 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH:12]=[O:13].[H-].[Na+].CI.[C:18](=O)(O)[O-].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:18])[CH:7]=[C:6]2[CH:12]=[O:13]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 827585-Methoxyindole-3-carbaldehydeHCID 516892Sodium Bicarbonate

Product 1

HCID 9259735-methoxy-1-methyl-1H-indole-3-carbaldehydeYield 99%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Methoxyindole-3-carboxaldehyde (300 mg, 1.71 mmol) was added in portions over 5 min to a suspension of sodium hydride (82 mg, 2.05 mmol, 60% dispersion in mineral oil) in DMF (8 mL) stirring under argon. The mixture was stirred for 30 min, methyl iodide (0.13 mL, 2.05 mmol) was added and the mixture was stirred for 1 h. Sodium bicarbonate (10%, 40 mL) was added and the mixture was extracted with EtOAc (4×). The combined organic layers were washed with sodium bicarbonate (10%, 2×) and saturated NaCl, dried (MgSO4), filtered and evaporated. Column chromatography of the crude product (50:50 EtOAc:hexanes) afforded 43 (320 mg, 99%) as a light yellow solid; Rf=0.35 (50:50 EtOAc:hexanes); mp=130-132° C.; lit mp=132-133° C.53; 1H NMR (CDCl3): δ 9.95 (s, 1H), 7.79 (d, 1H, J=2.4 Hz), 7.62 (s, 1H), 7.25 (d, J=8.8 Hz), 6.96 (dd, 1H, J=2.4 and 8.9 Hz), 3.90 (s, 3H), 3.85 (s, 3H).

Workup

  1. stirringThe mixture was stirred for 30 min
  2. stirringthe mixture was stirred for 1 h
  3. extractionthe mixture was extracted with EtOAc (4×)
  4. washThe combined organic layers were washed with sodium bicarbonate (10%, 2×) and saturated NaCl
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-07f2ad9f91d446ce89d8ac272f67b7d0
Source dataset
uspto-grants-2003_12
Patent number
US06656926B2

Linked notes

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