Potassium Carbonate → [6-Chloro-2-(4-methylpyridine-2-Carbonyl)-1H-indol-3-yl]acetic Acid

HRID 396433Notes

Reaction equation

HRID 396433 reaction equation
[Cl:1][C:2]1[CH:13]=[CH:12][C:5](/[CH:6]=[CH:7]/[C:8]([O:10]C)=[O:9])=[C:4]([NH:14][C:15](OCC)=O)[CH:3]=1.Br.BrC[C:23]([C:25]1[CH:30]=[C:29]([CH3:31])[CH:28]=[CH:27][N:26]=1)=[O:24].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]([C:6]([CH2:7][C:8]([OH:10])=[O:9])=[C:15]([C:23]([C:25]3[CH:30]=[C:29]([CH3:31])[CH:28]=[CH:27][N:26]=3)=[O:24])[NH:14]2)=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 23003310Methyl trans-4-chloro-2-(ethoxycarbonylamino)cinnamateHCID 230036032-Bromoacetyl4-methylpyridine hydrobromide

Product 1

HCID 9862267[6-Chloro-2-(4-methylpyridine-2-Carbonyl)-1H-indol-3-yl]acetic AcidYield 20%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of methyl trans-4-chloro-2-(ethoxycarbonylamino)cinnamate (step 1, 1.5 g, 5.3 mmol), 2-bromoacetyl-4-methylpyridine hydrobromide*, potassium carbonate (7.3 g, 53 mmol) and acetonitrile (50 ml) was heated at reflux temperature for 17 h. The mixture was then cooled and concentrated. The residue was diluted in ethyl acetate (200 ml) and washed with water (200 ml) and brine (200 ml). After drying (MgSO4) and removal of solvent, the crude product was purified by flash column chromatography eluting with ethyl acetate/hexane (1:5) to afford 433 mg (20%) of the title compound.

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 17 h
  3. temperatureThe mixture was then cooled
  4. concentrationconcentrated
  5. additionThe residue was diluted in ethyl acetate (200 ml)
  6. washwashed with water (200 ml) and brine (200 ml)
  7. customAfter drying
  8. custom(MgSO4) and removal of solvent
  9. customthe crude product was purified by flash column chromatography
  10. washeluting with ethyl acetate/hexane (1:5)

Sources & evidence

ORD record
ord-af0217dba22e449d8e83b3b5a261c044
Source dataset
uspto-grants-2003_08
Patent number
US06608070B1

Reaction notes

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