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

HRID 245231Notes

Reaction equation

HRID 245231 reaction equation
F[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]([O:25][CH3:26])=[O:24].[CH3:27][S-:28].[Na+].[H-].[Na+].CI>CN(C)C=O.O>[CH3:22][C:6]1[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)=[N:8][C:9]2[C:4]([C:5]=1[C:23]([O:25][CH3:26])=[O:24])=[CH:3][C:2]([S:28][CH3:27])=[CH:11][CH:10]=2

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 4378561Sodium methanethiolateHCID 67417240Methyl 6-fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 67417678Methyl 3-methyl-6-(methylthio)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 98.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of methyl 6-fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (2.4 g, 6.61 mmol) and sodium thiomethoxide (1.158 g, 16.52 mmol) in N,N-dimethylformamide (40 mL) was stirred at 100° C. overnight. The mixture was cooled to room temperature, treated with NaH (0.264 mg, 6.61 mmol), and stirred for 20 min. Methyl iodide (1.5 g, 9.92 mmol) was added, and the mixture was stirred for 2 h. The mixture was diluted with water and extracted with methylene chloride (three 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, 120 g Silica, 0-30% ethyl acetate/hexanes) to afford methyl 3-methyl-6-(methylthio)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (2.54 g, 95% yield). MS (m/z) 392.1 (M+H+).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. stirringstirred for 20 min
  3. stirringthe mixture was stirred for 2 h
  4. extractionextracted with methylene chloride (three times)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified via column chromatography (ISCO, 120 g Silica, 0-30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-96d6dab6b9944ce2a6e0a6c131e7a99c
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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