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

HRID 396434Notes

Reaction equation

HRID 396434 reaction equation
C[O:2][C:3](=[O:29])[CH2:4][CH:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[N:7](C(OCC)=O)[CH:6]1[C:20]([C:22]1[CH:27]=[C:26]([CH3:28])[CH:25]=[CH:24][N:23]=1)=[O:21].Cl>C(O)C.[OH-].[Na+]>[Cl:14][C:10]1[CH:9]=[C:8]2[C:13]([C:5]([CH2:4][C:3]([OH:29])=[O:2])=[C:6]([C:20]([C:22]3[CH:27]=[C:26]([CH3:28])[CH:25]=[CH:24][N:23]=3)=[O:21])[NH:7]2)=[CH:12][CH:11]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 23003422Methyl[6-chloro-1-ethoxycarbonyl-2-(4-methylpyridine-2-carbonyl)indolin-3-yl]acetate

Product 1

HCID 9862267[6-Chloro-2-(4-methylpyridine-2-Carbonyl)-1H-indol-3-yl]acetic AcidYield 17%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

A stirred solution of methyl[6-chloro-1-ethoxycarbonyl-2-(4-methylpyridine-2-carbonyl)indolin-3-yl]acetate (step 2, 930 mg, 2.2 mmol) in ethanol (20 ml) and 2N aqueous NaOH (10 ml) was heated at reflux temperature for 72 h. After cooling to room temperature, the resulting mixture was neutralized with 2N aqueous HCl (10 ml) and concentrated. The residue was diluted in dichloromethane/mehanol (10:1, 300 ml) and dried (MgSO4). After removal of solvent, the crude product was purified by flash column chromatography eluting with dichloromethane/methanol (20:1) and then washed with i-PrOH (ca.20 ml) to give 120 mg (17%) of the title compound as a yellow powder.

Workup

  1. temperatureat reflux temperature for 72 h
  2. concentrationconcentrated
  3. additionThe residue was diluted in dichloromethane/mehanol (10:1, 300 ml)
  4. dry with materialdried (MgSO4)
  5. customAfter removal of solvent
  6. customthe crude product was purified by flash column chromatography
  7. washeluting with dichloromethane/methanol (20:1)
  8. washwashed with i-PrOH (ca.20 ml)

Sources & evidence

ORD record
ord-203cc8c0c2b34764b0955384e0befef9
Source dataset
uspto-grants-2003_08
Patent number
US06608070B1

Reaction notes

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