Methyl iodide → 1-Methyl-1H-indole-5-carboxylic acid

HRID 1883207

Reaction equation

HRID 1883207 reaction equation
N1C2C(=CC(C(O)=O)=CC=2)C=C1.[H-].[Na+].IC.[CH3:17][N:18]1[C:26]2[C:21](=[CH:22][C:23]([C:27]([O:29]C)=[O:28])=[CH:24][CH:25]=2)[CH:20]=[CH:19]1.[OH-].[Na+]>CN(C=O)C.C1COCC1.CO.O>[CH3:17][N:18]1[C:26]2[C:21](=[CH:22][C:23]([C:27]([OH:29])=[O:28])=[CH:24][CH:25]=2)[CH:20]=[CH:19]1

Participants

10

Reactant 5

HCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 742801H-Indole-5-Carboxylic AcidHCID 10679201Methyl 1-methyl-1H-indole-5-carboxylate

Product 1

HCID 70156011-Methyl-1H-indole-5-carboxylic acidYield 96%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Under nitrogen atmosphere, a solution of indole-5-carboxylic acid (1.05 g) in DMF (40 mL) was cooled to 0° C., and thereto was added NaH (544 mg, 60%), and the mixture was stirred at the same temperature for 10 minutes, and stirred at room temperature for 30 minutes. The mixture was cooled to 0° C., and thereto was added iodomethane (3.68 g), and the mixture was stirred at room temperature for 48 hours. Water was added to the mixture, and the mixture was extracted three times with ethyl acetate-toluene, and dried over MgSO4. The solvent was evaporated under reduced pressure to give a crude methyl 1-methylindole-5-carboxylate. To a solution of the crude methyl 1-methylindole-5-carboxylate in THF (50 mL)-MeOH (50 mL) was added a 6N NaOH solution (5.4 mL), and the mixture was stirred at room temperature for 144 hours. The solvent was evaporated under reduced pressure. The residue was washed with ethyl acetate, and thereto was added a 6N aqueous hydrochloric acid solution to adjust the pH value thereof to pH=5-6. The mixture was extracted twice with ethyl acetate, and dried over MgSO4. The solvent was evaporated under reduced pressure to give 1-methyl-1H-indol-5-carboxylic acid (1.08 g, 96%).

Workup

  1. stirringstirred at room temperature for 30 minutes
  2. stirringthe mixture was stirred at room temperature for 48 hours
  3. extractionthe mixture was extracted three times with ethyl acetate-toluene
  4. dry with materialdried over MgSO4
  5. customThe solvent was evaporated under reduced pressure
  6. customto give a crude methyl 1-methylindole-5-carboxylate
  7. stirringthe mixture was stirred at room temperature for 144 hours
  8. customThe solvent was evaporated under reduced pressure
  9. washThe residue was washed with ethyl acetate
  10. additionwas added a 6N aqueous hydrochloric acid solution
  11. extractionThe mixture was extracted twice with ethyl acetate
  12. dry with materialdried over MgSO4
  13. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-6b914eadaa3c4d2ba35010d8d655f09f
Source dataset
uspto-grants-2004_07
Patent number
US06759429B2

Linked notes

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