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

HRID 58658Notes

Reaction equation

HRID 58658 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-d473822298564d648ffd63881c4b5945
Source dataset
uspto-grants-2016_09
Patent number
US09434722B2

Reaction notes

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