Hydrochloric Acid → HCID 18973447, compound

HRID 2394401Notes

Reaction equation

HRID 2394401 reaction equation
[H-].[Na+].[NH:3]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([CH:12]=[O:13])[C:6]=2[CH:5]=[CH:4]1.[C:14]([O:18][CH3:19])(=[O:17])[CH:15]=[CH2:16].[Cl-].[NH4+].Cl>CN(C)C=O>[CH3:19][O:18][C:14]([CH2:15][CH2:16][N:3]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([CH:12]=[O:13])[C:6]=2[CH:5]=[CH:4]1)=[O:17]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7294Methyl AcrylateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 333703Indole-4-carboxaldehyde

Product 1

HCID 18973447HCID 18973447, compoundYield 26.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Sodium hydride (95%; 383 mg) was suspended in 10 ml of dimethylformamide under an argon gas atmosphere. To the suspension, there was dropwise added a solution of 2.00 g of indole-4-carbaldehyde in 10 ml of dimethylformamide with ice-cooling and stirring. After stirring the reaction mixture at room temperature for 25 minutes, it was again ice-cooled followed by dropwise addition of a solution of 1.33 g of methyl acrylate in 10 ml of dimethylformamide and stirring at room temperature for 19 hours. The reaction system was poured into 400 ml of a 10% ammonium chloride solution, followed by addition of a 2% HCl aqueous solution till the system became acidic and extraction with ethyl acetate (200 ml×2). After drying the extract over anhydrous magnesium sulfate, the solvent was removed by distillation under reduced pressure and the resulting crude product was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to thus give 3.68 g of a pale yellow oily substance. This was dissolved in 40 ml of dimethylformamide, followed by addition of 2.70 g of methyl iodide and 2. 58 g of potassium carbonate and stirring the mixture at room temperature for 1.5 hour. The mixture was poured into 400 ml of a 10% ammonium chloride aqueous solution and extracted with ethyl acetate (200 ml×2). After drying the resulting extract over anhydrous sodium sulfate, the solvent was removed by distillation under reduced pressure and the resulting crude product was purified by silica gel column chromatography to give 848 mg of 1-(2-methoxycarbonylethyl)indole-4-carbaldehyde as a yellow oily substance. The yield thereof was found to be 27%.

Workup

  1. temperaturecooling
  2. stirringAfter stirring the reaction mixture at room temperature for 25 minutes
  3. temperaturecooled
  4. stirringstirring at room temperature for 19 hours
  5. extractionextraction with ethyl acetate (200 ml×2)
  6. customAfter drying the
  7. extractionextract over anhydrous magnesium sulfate
  8. customthe solvent was removed by distillation under reduced pressure
  9. customthe resulting crude product was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to thus give 3.68 g of a pale yellow oily substance
  10. dissolutionThis was dissolved in 40 ml of dimethylformamide
  11. additionfollowed by addition of 2.70 g of methyl iodide and 2
  12. stirring58 g of potassium carbonate and stirring the mixture at room temperature for 1.5 hour
  13. additionThe mixture was poured into 400 ml of a 10% ammonium chloride aqueous solution
  14. extractionextracted with ethyl acetate (200 ml×2)
  15. customAfter drying the resulting
  16. extractionextract over anhydrous sodium sulfate
  17. customthe solvent was removed by distillation under reduced pressure
  18. customthe resulting crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-8bbfeb626527496ba14085abd3ea264b
Source dataset
uspto-grants-1998_09
Patent number
US05811439

Reaction notes

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