Hydrochloric Acid → 3-(2-chloro-4-quinolinyl)-2,5-dimethyl-1H-indole-1-acetic acid

HRID 2354926Notes

Reaction equation

HRID 2354926 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:12]3[C:20]4[C:15](=[CH:16][CH:17]=[C:18]([CH3:21])[CH:19]=4)[NH:14][C:13]=3[CH3:22])=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:26][C:27]([O:29]CC)=[O:28].[ClH:32]>C1COCC1.CCO.[OH-].[Na+]>[Cl:32][C:8]1[CH:7]=[C:6]([C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([CH3:21])[CH:19]=3)[N:14]([CH2:26][C:27]([OH:29])=[O:28])[C:13]=2[CH3:22])[C:5]2[C:10](=[CH:11][CH:2]=[CH:3][CH:4]=2)[N:9]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 111625767-chloro-4-(2,5-dimethyl-1H-indol-3-yl)quinoline

Product 1

HCID 100902093-(2-chloro-4-quinolinyl)-2,5-dimethyl-1H-indole-1-acetic acid

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

7-chloro-4-(2,5-dimethyl-1H-indol-3-yl)quinoline (370 mg) was dissolved in dry THF (8 ml), and maintained under a nitrogen atmosphere. The reaction was cooled to −5° C. before slowly adding NaH (53 mg, 60% dispersion in mineral oil) portion-wise. Allowed the mixture to warm to RT and stirred for 40 minutes. The mixture was cooled to 0° C. before adding ethyl bromoacetate (0.147 ml) dropwise. After stirring for 1 hour at 15° C., the reaction was diluted with EtOH (5 ml) and 10% aqueous NaOH solution (3 ml). Stirring over night at RT converted the ethyl ester to the acid. Acidified with 1M aqueous HCl and extracted with EtOAc (×3). The combined organics were washed with water and brine then dried (Na2SO4) and the solvent was evaporated under reduced pressure. Further purification was by solid phase extraction using NH2 sorbent (6.5 g), eluting CH3CN and 20% AcOH/CH3CN. The solvent was evaporated under reduced pressure and the residue was azeotroped using toluene. This gave the title compound (378 mg).

Workup

  1. temperaturemaintained under a nitrogen atmosphere
  2. temperatureThe mixture was cooled to 0° C.
  3. stirringAfter stirring for 1 hour at 15° C.
  4. stirringStirring over night at RT
  5. extractionextracted with EtOAc (×3)
  6. washThe combined organics were washed with water and brine
  7. dry with materialthen dried (Na2SO4)
  8. customthe solvent was evaporated under reduced pressure
  9. customFurther purification
  10. extractionwas by solid phase extraction
  11. washeluting CH3CN and 20% AcOH/CH3CN
  12. customThe solvent was evaporated under reduced pressure
  13. customthe residue was azeotroped

Sources & evidence

ORD record
ord-4e6d8115bc5d426eade0c6a28ebb6c17
Source dataset
uspto-grants-2010_07
Patent number
US07754735B2

Reaction notes

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