Sodium Hydroxide → 6-Chloro-4-(3-chloro-phenyl)-2-cyclopropyl-quinoline-3-carboxylic acid

HRID 1497043Notes

Reaction equation

HRID 1497043 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH:12]1[CH2:14][CH2:13]1)[C:6]([C:15]([O:17]C)=[O:16])=[C:5]2[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=1.[OH-].[Na+]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH:12]1[CH2:14][CH2:13]1)[C:6]([C:15]([OH:17])=[O:16])=[C:5]2[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86682924Methyl 6-chloro-4-(3-chlorophenyl)-2-cyclopropylquinoline-3-carboxylate

Product 1

HCID 715562246-Chloro-4-(3-chloro-phenyl)-2-cyclopropyl-quinoline-3-carboxylic acidYield 74.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a white suspension of methyl 6-chloro-4-(3-chlorophenyl)-2-cyclopropylquinoline-3-carboxylate (45 mg, 0.12 mmol, 1 eq) in ethanol (2 ml) was added 1N NaOH (604 μl, 0.60 mmol, 5 eq) and the reaction mixture was refluxed overnight. The clear solution was then cooled to room temperature and concentrated in vacuo. The residue was diluted with water and the pH was adjusted to 3 with 1N HCl. The aqueous layer was extracted with ethyl acetate (×3) and the organic phases were combined and washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to give a crude residue which was purified by flash column chromatography (1:1 ethyl acetate:heptane with 5% AcOH) to give 6-chloro-4-(3-chloro-phenyl)-2-cyclopropyl-quinoline-3-carboxylic acid (32 mg, 74%) as a white solid. MS (ESI): 358.1 (M+H)+.

Workup

  1. temperaturethe reaction mixture was refluxed overnight
  2. concentrationconcentrated in vacuo
  3. additionThe residue was diluted with water
  4. extractionThe aqueous layer was extracted with ethyl acetate (×3)
  5. washwashed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a crude residue which
  10. customwas purified by flash column chromatography (1:1 ethyl acetate:heptane with 5% AcOH)

Sources & evidence

ORD record
ord-94552dc92c1c41e1a5fdbf25056e62f3
Source dataset
uspto-grants-2015_12
Patent number
US09199938B2

Reaction notes

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