Acrylic Acid → 5-Methyl-1H-indole-3-propanoic acid

HRID 1058957Notes

Reaction equation

HRID 1058957 reaction equation
[C:1]([OH:5])(=[O:4])[CH:2]=[CH2:3].[CH3:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]=[CH:10]2.[OH-].[Na+]>C(O)(=O)C.C(OC(=O)C)(=O)C>[CH3:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]=[C:10]2[CH2:3][CH2:2][C:1]([OH:5])=[O:4]

Participants

6

Reactant 3

HCID 6581Acrylic AcidHCID 119785-MethylindoleHCID 14798Sodium Hydroxide

Product 1

HCID 186690955-Methyl-1H-indole-3-propanoic acidYield 43%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 7918Acetic AnhydrideSolvent

Procedure

Acrylic acid (16.5 mL, 240.6 mmol) was added to a solution of 5-methyl-1H-indole (10.5 g, 80.2 mmol) in acetic acid (20 mL) and acetic anhydride (20 mL) and the mixture was stirred at room temperature for 1 week. Aqueous sodium hydroxide (4N, 100 mL) was added and the mixture was washed with ethyl acetate. The aqueous fraction was acidified to pH 1 with hydrochloric acid (5M) and extracted with ethyl acetate. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure to give the title compound as a brown solid (7 g, 43%). 1H NMR (360MHz, CDCl3) δ7.85 (1H, br s), 7.38 (1H, s), 7.24 (1H, d, J 8.3 Hz), 7.02 (1H, dd, J 8.3, 2.3 Hz), 6.97 (1H, d, J 2.3 Hz), 3.09 (2H, t, J 7.6 Hz), 2.76 (2H, t, J 7.6 Hz), and 2.46 (3H, s).

Workup

  1. washthe mixture was washed with ethyl acetate
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic fractions were dried (MgSO4)
  4. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-ca1945c6f2ba484a8ec03b96267918ae
Source dataset
uspto-grants-2003_02
Patent number
US06518273B1

Reaction notes

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