Water → 5-Methoxy-3-methoxycarbonyl-2-methoxymethyl-1-methylindole

HRID 2225884Notes

Reaction equation

HRID 2225884 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[C:6]([CH2:12][O:13][CH3:14])=[C:5]2[C:15]([O:17][CH3:18])=[O:16].[H-].[Na+].[CH3:21]I.O>CN(C)C=O>[CH3:21][O:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[C:6]([CH2:12][O:13][CH3:14])=[C:5]2[C:15]([O:17][CH3:18])=[O:16]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 10198835methyl 5-hydroxy-2-(methoxymethyl)-1-methylindole-3-carboxylate

Product 1

HCID 106591965-Methoxy-3-methoxycarbonyl-2-methoxymethyl-1-methylindoleYield 89.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

14.9 g of 5-hydroxy-3-methoxycarbonyl-2-methoxymethyl-1-methylindole (59.8 mmol) obtained in Example 1 was dissolved in 150 ml of anhydrous dimethylformamide, and the solution was stirred in a stream of nitrogen under ice cooling. To this were added 2.63 g (65.8 mmol) of sodium hydride (60% oil dispersion) and 4.1 ml (65.9 mmol) of methyl iodide in that order. After 2 hours of heating at 50° C., the resulting reaction mixture was cooled down, mixed with water and then extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated sodium chloride aqueous solution and then dried over anhydrous magnesium sulfate. After anhydrous magnesium sulfate was filtered off and the solvent was distilled off under reduced pressure, the resulting residue was purified by a silica gel column chromatography (eluent: hexane-ethyl acetate, 3:1) to obtain 14.1 g of the title compound with a yield of 89%.

Workup

  1. customthe resulting reaction mixture
  2. temperaturewas cooled down
  3. extractionextracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with water and saturated sodium chloride aqueous solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationAfter anhydrous magnesium sulfate was filtered off
  7. distillationthe solvent was distilled off under reduced pressure
  8. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane-ethyl acetate, 3:1)

Sources & evidence

ORD record
ord-eb0537d5274c4574b6c1c7f9c71f8041
Source dataset
uspto-grants-1994_09
Patent number
US05344938

Reaction notes

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