Methanol → Methyl 6-fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

HRID 245230Notes

Reaction equation

HRID 245230 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=1)[C:6]([CH3:22])=[C:5]2[C:23]([OH:25])=[O:24].[C:26](Cl)(=O)C(Cl)=O.CO>CN(C=O)C.ClCCl>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:19])[F:20])[CH:13]=1)[C:6]([CH3:22])=[C:5]2[C:23]([O:25][CH3:26])=[O:24]

Participants

6

Reactant 3

HCID 887MethanolHCID 65578Oxalyl chlorideHCID 673838086-Fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

Product 1

HCID 67417240Methyl 6-fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 82.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

DMF (5 drops) was added to a suspension of 6-fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (11.2 g, 32.1 mmol) in dichloromethane (120 mL) at 0° C. Oxalyl chloride (4.21 mL, 48.1 mmol) was added slowly. The mixture was stirred at 0° C. for 1 h. Methanol (30 mL) was added to the mixture, the mixture was stirred at 0° C. for 2 h and warmed to room temperature overnight. The solvent was removed under reduced pressure, and the residue was diluted with water and treated with saturated aqueous NaHCO3 until basic. The aqueous mixture was extracted with methylene chloride (three times). The combined organic phases were washed with brine (two times), dried over Na2SO4, filtered, and concentrated. The residue was purified via column chromatography (ISCO, 120 g Silica, 0-30% ethyl acetate/hexanes) to give methyl 6-fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (9.6 g, 82% yield). MS (m/z) 364.1 (M+H+).

Workup

  1. stirringthe mixture was stirred at 0° C. for 2 h
  2. temperaturewarmed to room temperature overnight
  3. customThe solvent was removed under reduced pressure
  4. additionthe residue was diluted with water
  5. additiontreated with saturated aqueous NaHCO3 until basic
  6. extractionThe aqueous mixture was extracted with methylene chloride (three times)
  7. washThe combined organic phases were washed with brine (two times)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified via column chromatography (ISCO, 120 g Silica, 0-30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-48b84a8636044bd39231f8b26bfc9bac
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

Loading…