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

HRID 245201Notes

Reaction equation

HRID 245201 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. The mixture was stirred at 0° C. for 1 h. MeOH (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. The residue was diluted with water, treated with saturated aqueous NaHCO3, and extracted with methylene chloride. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified via column chromatography (ISCO, 330 g silica, 40-100% methylene chloride/hexanes) to afford methyl 6-bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (29.8 g, 68% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.05 (s, 1H), 7.96-8.01 (m, 2H), 7.89 (d, J=7.78 Hz, 1H), 7.77 (t, J=7.65 Hz, 1H), 7.65 (s, 1H), 4.08 (s, 3H), 4.03 (s, 3H), 2.34 (s, 3H); 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
  5. additiontreated with saturated aqueous NaHCO3
  6. extractionextracted with methylene chloride
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude material was purified via column chromatography (ISCO, 330 g silica, 40-100% methylene chloride/hexanes)

Sources & evidence

ORD record
ord-5e139e52441743968d98fa9411249d93
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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