Sulfuric Acid → HCID 22490527, compound

HRID 2180868Notes

Reaction equation

HRID 2180868 reaction equation
Cl.[C:2]1([CH3:10])[CH:7]=[CH:6][CH:5]=[C:4]([NH:8]N)[CH:3]=1.[C:11]([OH:18])(=[O:17])[CH2:12][CH2:13][C:14]([CH3:16])=O.S(=O)(=O)(O)O>O>[CH3:16][C:14]1[NH:8][C:4]2[C:5]([C:13]=1[CH2:12][C:11]([OH:18])=[O:17])=[CH:6][CH:7]=[C:2]([CH3:10])[CH:3]=2

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 11579Levulinic AcidHCID 71562m-Tolylhydrazinium(1+) chloride

Product 1

HCID 22490527HCID 22490527, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-tolylhydrazine hydrochloride (1 g), levulinic acid (1.3 g) and 10% aqueous sulfuric acid (20 ml) was stirred for 6 hours under a nitrogen atmosphere at 80° C. The reaction mixture was allowed to cool, water was added, and then extraction was performed with ethyl acetate and the organic layer was concentrated under reduced pressure. Saturated sodium bicarbonate was added to the obtained residue and vigorously stirred therewith, and then dichloromethane was added and the mixture was again vigorously stirred. The aqueous layer was collected, rendered acidic with concentrated aqueous hydrochloric acid, and then extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. Methanol (20 ml) and concentrated sulfuric acid (1 ml) were added to the obtained residue, and the mixture was heated to reflux for 2 hours. The reaction mixture was allowed to cool, water was added, and then extraction was performed with dichloromethane. The organic layer was collected and dried over sodium sulfate, and then concentrated under reduced pressure. A 2-(2,6-dimethyl-1H-indol-3-yl)acetic acid methyl ester component was purified from the obtained residue by silica gel column chromatography using a mixed solvent of hexane and ethyl acetate. A 2 N sodium hydroxide aqueous solution (10 ml) and methanol (10 ml) were added to the obtained 2-(2,6-dimethyl-1H-indol-3-yl)acetic acid methyl ester, and the mixture was heated to reflux for one hour. The reaction mixture was allowed to cool, water was added, and then the mixture was rendered acidic with concentrated aqueous hydrochloric acid and extracted with ethyl acetate. The organic layer was collected and dried over sodium sulfate, and then concentrated under reduced pressure to obtain 0.13 g of the title compound as a colorless powder (13% yield).

Workup

  1. temperatureto cool
  2. extractionextraction
  3. concentrationthe organic layer was concentrated under reduced pressure
  4. additionSaturated sodium bicarbonate was added to the obtained residue
  5. stirringvigorously stirred
  6. additiondichloromethane was added
  7. stirringthe mixture was again vigorously stirred
  8. customThe aqueous layer was collected
  9. extractionextracted with ethyl acetate
  10. dry with materialThe organic layer was dried over sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. additionMethanol (20 ml) and concentrated sulfuric acid (1 ml) were added to the obtained residue
  13. temperaturethe mixture was heated
  14. temperatureto reflux for 2 hours
  15. temperatureto cool
  16. additionwater was added
  17. extractionextraction
  18. customThe organic layer was collected
  19. dry with materialdried over sodium sulfate
  20. concentrationconcentrated under reduced pressure
  21. customA 2-(2,6-dimethyl-1H-indol-3-yl)acetic acid methyl ester component was purified from the obtained residue by silica gel column chromatography
  22. additionA 2 N sodium hydroxide aqueous solution (10 ml) and methanol (10 ml) were added to the obtained 2-(2,6-dimethyl-1H-indol-3-yl)acetic acid methyl ester
  23. temperaturethe mixture was heated
  24. temperatureto reflux for one hour
  25. temperatureto cool
  26. additionwater was added
  27. extractionextracted with ethyl acetate
  28. customThe organic layer was collected
  29. dry with materialdried over sodium sulfate
  30. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8dadab2fc9dc4fd98d2fb9ead60f3f7e
Source dataset
uspto-grants-2005_05
Patent number
US06887890B2

Reaction notes

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