Citric Acid → HCID 71556352, compound

HRID 1497073Notes

Reaction equation

HRID 1497073 reaction equation
C[O:2][C:3]([C:5]1[C:6]([CH:27]([CH3:29])[CH3:28])=[N:7][C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][C:22]([F:25])([F:24])[F:23])[CH:16]=1)=[CH:12][C:11]([Cl:26])=[CH:10][CH:9]=2)=[O:4].[I-].[Li+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>N1C=CC=CC=1.O.C(OCC)(=O)C>[Cl:26][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][CH:10]=1)[N:7]=[C:6]([CH:27]([CH3:28])[CH3:29])[C:5]([C:3]([OH:4])=[O:2])=[C:14]2[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][C:22]([F:24])([F:23])[F:25])[CH:16]=1

Participants

7

Reactant 3

HCID 311Citric AcidHCID 66321Lithium iodideHCID 86682939HCID 86682939, compound

Product 1

HCID 71556352HCID 71556352, compoundYield 52%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the stirred solution of 6-chloro-2-isopropyl-4-(3-trifluoromethoxy-phenyl)-quinoline-3-carboxylic acid methyl ester (50 mg, 0.118 mmol) in 3 ml of pyridine under nitrogen was added lithium iodide (158 mg, 1.18 mmol) at RT. Then the reaction mixture was refluxed for 16 h. Volatiles were removed under vacuo to afford a crude residue which was diluted with water and ethyl acetate. The organic phase was discarded and the aqueous layer was made acidic to pH 3 with 10% aqueous citric acid under cooling. The aqueous phase was then extracted with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo to give a crude residue which was purified by prep TLC (mobile phase: 5% MeOH in DCM) to afford 6-chloro-2-isopropyl-4-(3-trifluoromethoxy-phenyl)-quinoline-3-carboxylic acid (25 mg, 52%) as an off white solid. LC-MS: 410 (M+H)+.

Workup

  1. temperatureThen the reaction mixture was refluxed for 16 h
  2. customVolatiles were removed under vacuo
  3. customto afford a crude residue which
  4. temperatureunder cooling
  5. extractionThe aqueous phase was then extracted with ethyl acetate
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customto give a crude residue which
  10. customwas purified by prep TLC (mobile phase: 5% MeOH in DCM)

Sources & evidence

ORD record
ord-29c23b3e574b43738f80adfdcc5340c3
Source dataset
uspto-grants-2015_12
Patent number
US09199938B2

Reaction notes

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