Potassium Carbonate → 6-Chloro-2-(4-chlorobenzoyl)indol-3-acetic acid

HRID 396573Notes

Reaction equation

HRID 396573 reaction equation
C([O:3][C:4](=[O:25])[CH:5]=[CH:6][C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=1[NH:14]S(C1C=CC(C)=CC=1)(=O)=O)C.C(=O)([O-])[O-].[K+].[K+].Br[CH2:33][C:34]([C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=1)=[O:35].[OH-].[Na+]>CN(C)C(=O)C>[Cl:13][C:10]1[CH:9]=[C:8]2[C:7]([C:6]([CH2:5][C:4]([OH:3])=[O:25])=[C:33]([C:34](=[O:35])[C:36]3[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=3)[NH:14]2)=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 68303p-Chlorophenacyl bromideHCID 53985536HCID 53985536, compound

Product 1

HCID 97983746-Chloro-2-(4-chlorobenzoyl)indol-3-acetic acidYield 82%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of 3-[4-chloro-2-(toluene-4-sulfonylamino)-phenyl]-acrylic acid ethyl ester (13.0g, 34.2 mmol) in N,N-dimethylacetamide (120 ml) was added potassium carbonate (9.45 g, 68.4 mmol) and 2-bromo-4′-chloroacetophenone (8.78 g, 37.6 mmol) and the reaction was stirred at room temperature for 15 minutes. 1N Sodium hydroxide (130 ml) was added and the reaction mixture was heated to 100° C. for 8 hours. The reaction mixture was cooled to room temperature and poured into a separatory funnel and washed with methyl t-butyl ether (2×200 ml). The aqueous layer was acidified to pH 1 with 6N hydrochloric acid and was extracted with ethyl acetate (150 ml). The solvent was removed under reduced pressure and to the resulting oil was added isopropyl alcohol (24 ml) and water (48 ml). A solid precipitated and the slurry was stirred 12 hours. The precipitate was filtered, washed with water, and dried to provide [6-chloro-2-(4-chloro-benzoyl)-1H-indol-3-yl]-acetic acid (9.73 g, 82%). mp 181-183° C. 1H NMR (400 MHz, d6-DMSO) d 3.79 (s, 2), 7.08 (dd, 1, J=8.5, 1.9), 7.42 (d, 1, J=1.9), 7.60 (d, 2, J=8.5), 7.62-7.73 (m, 3), 11.74 (bs, 1), 12.22 (bs, 1). 13C NMR (75 MHz, d6-DMSO) d 31.74, 113.25, 118.00, 121.93, 123.96, 127.69, 130.10, 131.30, 132.02, 133.59, 138.02, 138.37, 138.58, 173.20, 188.29. IR 3314, 1710, 1700, 1618, 1522, 1323, 1227, 1093, 941 cm−1. Analysis calculated for C17H11Cl2NO3: C, 58.64; H, 3.18; N, 4.02. Found: C, 58.58; H, 3.22; N, 3.93.

Workup

  1. temperaturethe reaction mixture was heated to 100° C. for 8 hours
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additionpoured into a separatory funnel
  4. washwashed with methyl t-butyl ether (2×200 ml)
  5. extractionwas extracted with ethyl acetate (150 ml)
  6. customThe solvent was removed under reduced pressure and to the resulting oil
  7. additionwas added isopropyl alcohol (24 ml) and water (48 ml)
  8. customA solid precipitated
  9. stirringthe slurry was stirred 12 hours
  10. filtrationThe precipitate was filtered
  11. washwashed with water
  12. customdried

Sources & evidence

ORD record
ord-558cbae2079246d288c628255f0e9e66
Source dataset
uspto-grants-2003_08
Patent number
US06608070B1

Reaction notes

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