Acrylic Acid → 1H-Indole-3-propanoic acid, 5-chloro-

HRID 1918647Notes

Reaction equation

HRID 1918647 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[C:11]([OH:15])(=[O:14])[CH:12]=[CH2:13].C(OC(=O)C)(=O)C>C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:13][CH2:12][C:11]([OH:15])=[O:14]

Participants

5

Reactant 3

HCID 6581Acrylic AcidHCID 7918Acetic AnhydrideHCID 871105-Chloroindole

Product 1

HCID 1857801H-Indole-3-propanoic acid, 5-chloro-Yield 24.4%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-chloro-1H-indole (2.5 g; 16.49 mmol), acrylic acid (2.49 mL; 36.28 mmol) and acetic anhydride (3.09 mL; 32.98 mmol) in acetic acid was stirred at 100° C. for 48 hours, concentrated under reduced pressure and diluted in NaOH 3N (water), the precipitate was filtered off and the solution acidified to pH 2 and extracted with dichloromethane. The organic phase was dried and concentrated under reduced pressure and the crude material was purified by flash chromatography on silica gel (eluent: 2 to 20% of ethyl acetate in dichloromethane) and (eluent: 15 to 60% of ethyl acetate in heptane) to give 0.900 g (24%) of 3-(5-chloro-1H-indol-3-yl)propanoic acid as a brown solid.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additiondiluted in NaOH 3N (water)
  3. filtrationthe precipitate was filtered off
  4. extractionextracted with dichloromethane
  5. customThe organic phase was dried
  6. concentrationconcentrated under reduced pressure
  7. customthe crude material was purified by flash chromatography on silica gel (eluent: 2 to 20% of ethyl acetate in dichloromethane) and (eluent: 15 to 60% of ethyl acetate in heptane)

Sources & evidence

ORD record
ord-108d9db963b44c3d8116428a4c70c6d1
Source dataset
uspto-grants-2013_12
Patent number
US08618138B2

Reaction notes

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