Indole-3-Acetic Acid → HCID 16234827, compound

HRID 1614197Notes

Reaction equation

HRID 1614197 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]([OH:13])=O)=[CH:2]1.[C:14]([O:23][CH3:24])(=[O:22])[C:15]1[C:16](=[CH:18][CH:19]=[CH:20][CH:21]=1)[NH2:17].CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>C1COCC1>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]([NH:17][C:16]2[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=2[C:14]([O:23][CH3:24])=[O:22])=[O:13])=[CH:2]1

Participants

5

Reactant 3

HCID 802Indole-3-Acetic AcidHCID 8635Methyl AnthranilateHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)

Product 1

HCID 16234827HCID 16234827, compoundYield 86.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

[Route A/E modified To a solution of 3-indoleacetic acid (5.79 g, 33.1 mmol) in 100 ml THF at room temperature was added 1,1-carbonyldiimidazole (5.36 g, 33.1 mmol). The reaction mixture was stirred for 15 minutes under nitrogen. Methyl anthranilate (5.0 g, 33.1 mmol) and PPTS (20.0 g, 80 mmol) were added to the reaction mixture which was then stirred at reflux for 24 hours, cooled, and concentrated to near dryness in vacuo. The product residue was partitioned between 1N hydrochloric acid and ethyl acetate. The two-phase mixture was heated until two clear layers were obtained. The aqueous layer was separated and the organic layer was allowed to cool, washed (water, 1N NaOH, and brine), dried over anhydrous sodium sulfate, and concentrated in vacuo to dryness. The resulting product was triturated with ethyl acetate/hexane and collected by vacuum-assisted filtration to give 8.85 g of 2-(3-indolyl)-N-(2-methoxycarbonylphenyl)acetamide as a pale yellow granular solid which was deesterified by refluxing it in a mixture of 100 ml of methanol and 32 ml of 1M NaOH for 30 minutes. The product acid was isolated by concentrating the deesterification mixture in vacuo, acidifying with 40 ml of 1N hydrochloric acid, and then extracting it into ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo to dryness. Trituration with ethyl acetate/hexanes and vacuum-assisted filtration provided 8.0 g of 2-(3-indolyl)-N-(2-carboxyphenyl)acetamide as an off-white solid: mp 205°-207° C.

Workup

  1. stirringwas then stirred
  2. temperatureat reflux for 24 hours
  3. temperaturecooled
  4. concentrationconcentrated
  5. customThe product residue was partitioned between 1N hydrochloric acid and ethyl acetate
  6. temperatureThe two-phase mixture was heated until two clear layers
  7. customwere obtained
  8. customThe aqueous layer was separated
  9. temperatureto cool
  10. washwashed (water, 1N NaOH, and brine)
  11. dry with materialdried over anhydrous sodium sulfate
  12. concentrationconcentrated in vacuo to dryness
  13. customThe resulting product was triturated with ethyl acetate/hexane
  14. filtrationcollected by vacuum-assisted filtration

Sources & evidence

ORD record
ord-a3373a60e7ab449c979cd07fe70fbccb
Source dataset
uspto-grants-1993_03
Patent number
US05196427

Reaction notes

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