Methanol → Methyl 6-bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

HRID 245259Notes

Reaction equation

HRID 245259 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[C:7]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=1)[C:6]([CH3:24])=[C:5]2[C:25]([OH:27])=[O:26].[C:28](Cl)(=O)C(Cl)=O.CO>CN(C=O)C.ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[C:7]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:21])[F:22])[CH:15]=1)[C:6]([CH3:24])=[C:5]2[C:25]([O:27][CH3:28])=[O:26]

Participants

6

Reactant 3

HCID 887MethanolHCID 65578Oxalyl chlorideHCID 673838286-Bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

Product 1

HCID 67384067Methyl 6-bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 68%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

DMF (5 drops) was added to a suspension of 6-bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (42.6 g, 97 mmol) in dichloromethane (500 mL) at 0° C. Oxalyl chloride (12.71 mL, 145 mmol) was added slowly, and the mixture was stirred at 0° C. for 1 h. Methanol (30 mL) was added, and the resulting mixture was stirred at 0° C. for 2 h and allowed to warm to room temperature overnight. The solvent was removed under reduced pressure, and the residue was diluted with water and neutralized with saturated aqueous NaHCO3. The mixture was extracted with methylene chloride, and the organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified via column chromatography (ISCO, 330 g silica, 40-100% methylene chloride/hexanes) to give methyl 6-bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (29.8 g, 68% yield). MS (m/z) 455.0 (M+H+).

Workup

  1. stirringthe resulting mixture was stirred at 0° C. for 2 h
  2. temperatureto warm to room temperature overnight
  3. customThe solvent was removed under reduced pressure
  4. additionthe residue was diluted with water and neutralized with saturated aqueous NaHCO3
  5. extractionThe mixture was extracted with methylene chloride
  6. washthe organic extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified via column chromatography (ISCO, 330 g silica, 40-100% methylene chloride/hexanes)

Sources & evidence

ORD record
ord-9e28ca55e65c488fa73f310a841d2983
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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