Triethylamine → Methyl 3-methyl-6-(methylthio)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

HRID 245153

Reaction equation

HRID 245153 reaction equation
[CH3:1][C:2]1[C:3]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=2)=[N:4][C:5]2[C:10]([C:11]=1[C:12]([OH:14])=[O:13])=[CH:9][C:8]([S:15][CH3:16])=[CH:7][CH:6]=2.[C:27](Cl)(=O)C(Cl)=O.C(N(CC)CC)C>CN(C=O)C.ClCCl>[CH3:1][C:2]1[C:3]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:24])[F:25])[CH:18]=2)=[N:4][C:5]2[C:10]([C:11]=1[C:12]([O:14][CH3:27])=[O:13])=[CH:9][C:8]([S:15][CH3:16])=[CH:7][CH:6]=2

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 674183523-Methyl-6-(methylthio)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

Product 1

HCID 67417678Methyl 3-methyl-6-(methylthio)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 69%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

DMF (5 drops) was added to a suspension of 3-methyl-6-(methylthio)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (2.1 g, 5.56 mmol) in dichloromethane (100 mL). Oxalyl chloride (0.731 mL, 8.35 mmol) was added slowly and the mixture was stirred for 1 h. The solvent was removed under reduced pressure, the residue was redissolved in methanol (50 mL), and triethylamine (1.55 mL, 11.13 mmol) was added slowly. The mixture was stirred overnight at room temperature. The solvent was removed under reduced pressure, the residue was diluted with aqueous saturated NaHCO3, and the aqueous mixture was extracted with ethyl acetate (3 times). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified via column chromatography (ISCO, 0-30% ethyl acetate/hexanes) to give methyl 3-methyl-6-(methylthio)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.5 g, 69% yield). 1H NMR (400 MHz, DMSO-d6) δ 7.95-8.04 (m, 3H), 7.88 (d, J=8.03 Hz, 1H), 7.69-7.81 (m, 2H), 7.41 (d, J=2.01 Hz, 1H), 4.08 (s, 3H), 2.62 (s, 3H), 2.35 (s, 3H); MS (m/z) 392.1 (M+H+).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was redissolved in methanol (50 mL)
  3. stirringThe mixture was stirred overnight at room temperature
  4. customThe solvent was removed under reduced pressure
  5. additionthe residue was diluted with aqueous saturated NaHCO3
  6. extractionthe aqueous mixture was extracted with ethyl acetate (3 times)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified via column chromatography (ISCO, 0-30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f7c4ebcf19434ec9b187d1e770eaefb8
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Linked notes

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