Methyl-6-methoxy-2-indolecarboxylate → 6-methoxy-2-methyl-1H-indole

HRID 502138Notes

Reaction equation

HRID 502138 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH3:7][O:8][C:9]1[CH:17]=[C:16]2[C:12]([CH:13]=[C:14]([C:18](OC)=O)[NH:15]2)=[CH:11][CH:10]=1>O1CCOCC1>[CH3:7][O:8][C:9]1[CH:17]=[C:16]2[C:12]([CH:13]=[C:14]([CH3:18])[NH:15]2)=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 688173Methyl-6-methoxy-2-indolecarboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 108447096-methoxy-2-methyl-1H-indoleYield 61%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a suspension of LiAlH4 (7.6 g, 0.2 mol) in dioxane (100 mL) is added dropwise a solution of methyl 6-methoxy-1H-indole-2-carboxylate (8.2 g, 0.04 mol) in dioxane (50 mL) at 0° C. After the addition, the mixture is stirred at room temperature for 1 h and then heated at reflux for 5 h. After cooling to 0° C., the reaction is quenched by water (dropwise) and then 15% aqueous NaOH. After stirring at room temperature for 1 h, the mixture is filtered through Celite. The solid is washed with a large amount of EtOAc. The solvent is washed with brine, dried over Na2SO4 and evaporated under vacuum. The residue is purified by flash column chromatography on silica gel using EtOAc/petroleum ether (1/5) as eluent to yield 61% of 6-methoxy-2-methyl-1H-indole.

Workup

  1. additionAfter the addition
  2. temperatureheated
  3. temperatureat reflux for 5 h
  4. temperatureAfter cooling to 0° C.
  5. customthe reaction is quenched by water (dropwise) and then 15% aqueous NaOH
  6. stirringAfter stirring at room temperature for 1 h
  7. filtrationthe mixture is filtered through Celite
  8. washThe solid is washed with a large amount of EtOAc
  9. washThe solvent is washed with brine
  10. dry with materialdried over Na2SO4
  11. customevaporated under vacuum
  12. customThe residue is purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-88d886f9e40848cf9a77ef484c93c214
Source dataset
uspto-grants-2010_08
Patent number
US07772271B2

Reaction notes

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