Dimethylformamide → Methyl 3-methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

HRID 245246Notes

Reaction equation

HRID 245246 reaction equation
[CH3:1][C:2]1[C:3]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)=[N:4][C:5]2[C:10]([C:11]=1[C:12]([OH:14])=[O:13])=[CH:9][C:8]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:7][CH:6]=2.[C:29](Cl)(=O)C(Cl)=O.CN(C)C=O>CO>[CH3:1][C:2]1[C:3]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:26])[F:27])[CH:20]=2)=[N:4][C:5]2[C:10]([C:11]=1[C:12]([O:14][CH3:29])=[O:13])=[CH:9][C:8]([S:15]([CH3:18])(=[O:16])=[O:17])=[CH:7][CH:6]=2

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 673841653-Methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

Product 1

HCID 67383507Methyl 3-methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 63.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 3-methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (4.07 g, 9.94 mmol) at 0° C. was added oxalyl chloride (1.305 mL, 14.91 mmol) and N,N-dimethylformamide (0.1 mL). The resulting mixture was stirred at 0° C. for 1 h. Methanol (5 mL) was added, and the mixture was warmed to room temperature and stirred overnight. The solvent was removed under reduced pressure, and the residue diluted with saturated aqueous NaHCO3. The aqueous mixture was extracted with methylene chloride, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was absorbed onto florisil and purified via column chromatography (ISCO, 5-100% ethyl acetate/hexanes) to afford methyl 3-methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (2.665 g, 60% yield). MS (m/z) 424.0 (M+H+).

Workup

  1. temperaturethe mixture was warmed to room temperature
  2. stirringstirred overnight
  3. customThe solvent was removed under reduced pressure
  4. additionthe residue diluted with saturated aqueous NaHCO3
  5. extractionThe aqueous mixture was extracted with methylene chloride
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was absorbed onto florisil
  10. custompurified via column chromatography (ISCO, 5-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f60b55e54b8240cf98e02f453892b9f3
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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