Diethyl Ether → 3-[5-chloro-2-(4-chlorophenyl)-1H-indol-3-yl]propanoic Acid

HRID 1016649Notes

Reaction equation

HRID 1016649 reaction equation
C(N(CC)CC)C.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=O)[CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20])=[CH:11][CH:10]=1.Cl.[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31]N)=[CH:27][CH:26]=1.CCOCC>C(O)C>[Cl:24][C:25]1[CH:26]=[C:27]2[C:28](=[CH:29][CH:30]=1)[NH:31][C:15]([C:12]1[CH:13]=[CH:14][C:9]([Cl:8])=[CH:10][CH:11]=1)=[C:16]2[CH2:17][CH2:18][C:19]([OH:21])=[O:20]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 71600Hydrazine, (4-chlorophenyl)-, hydrochloride (1:1)HCID 27337165-(4-Chlorophenyl)-5-oxopentanoic acid

Product 1

HCID 97977463-[5-chloro-2-(4-chlorophenyl)-1H-indol-3-yl]propanoic AcidYield 65%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Triethylamine (5 mL, 3.6 g, 36 mmol) was added dropwise to a stirred suspension of 4-chloro-δ-oxobenzenepentanoic acid (7.91 g, 35 mmol) and (4-chlorophenyl)hydrazine hydrochloride (6.29 g, 35 mmol) in ethanol (54 mL) and the mixture was stirred at room temperature for 3 h. Ether (500 mL) was added, the mixture was filtered and the solvent was evaporated under reduced pressure. The residue was added slowly to trifluoroacetic acid (120 mL) and the mixture was heated under reflux for 2 h. The mixture was cooled, water (250 mL) was added and the mixture was extracted with ethyl acetate (300 mL). The organic fraction was washed with brine (30 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was recrystallized from EtOAc/isohexane to give the title compound (7.6 g, 65%). 1H NMR (250 MHz, DMSO-d6) δ 12.01 (1H, br s), 11.36 (1H, s), 7.56-7.47 (5H, m), 7.26 (1H, d, J 8.5 Hz), 7.01 (1H, dd, J 8.5, 2.0 Hz), 2.96 (2H, t, 8.0 Hz), and 2.43 (2H, t, 8.0 Hz).

Workup

  1. filtrationthe mixture was filtered
  2. customthe solvent was evaporated under reduced pressure
  3. additionThe residue was added slowly to trifluoroacetic acid (120 mL)
  4. temperaturethe mixture was heated
  5. temperatureunder reflux for 2 h
  6. temperatureThe mixture was cooled
  7. additionwater (250 mL) was added
  8. extractionthe mixture was extracted with ethyl acetate (300 mL)
  9. washThe organic fraction was washed with brine (30 mL)
  10. dry with materialdried (MgSO4)
  11. customthe solvent was evaporated under reduced pressure
  12. customThe residue was recrystallized from EtOAc/isohexane

Sources & evidence

ORD record
ord-fc3642d4cdf94cab9f4e27168e28f902
Source dataset
uspto-grants-2002_11
Patent number
US06476045B2

Reaction notes

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