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

HRID 245181

Reaction equation

HRID 245181 reaction equation
[H-].[Na+].F[C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[N:10]=[C:9]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=1)[C:8]([CH3:26])=[C:7]2[C:27]([OH:29])=[O:28].[CH3:30][S-:31].[Na+].I[CH3:34]>CS(C)=O.CCOCC>[CH3:26][C:8]1[C:9]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:23])([F:25])[F:24])[CH:17]=2)=[N:10][C:11]2[C:6]([C:7]=1[C:27]([O:29][CH3:34])=[O:28])=[CH:5][C:4]([S:31][CH3:30])=[C:13]([O:14][CH3:15])[CH:12]=2

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 4378561Sodium methanethiolateHCID 673840026-Fluoro-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

Product 1

HCID 67383617Methyl 3-methyl-7-(methyloxy)-6-(methylthio)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 82.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
100 °C

Procedure

Sodium hydride (0.949 g, 23.73 mmol) was added portionwise to a suspension of 6-fluoro-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (6.0 g, 15.82 mmol) in dimethyl sulfoxide (50 mL). After 20 min, sodium thiomethoxide (1.44 g, 17.40 mmol) was added. The reaction mixture was heated to 100° C. for 2 h. The mixture was cooled to room temperature and iodomethane (4.95 mL, 79 mmol) was added. The reaction mixture was stirred for 2 h, diluted with ether, and extracted with methylene chloride (three times). The combined organic extracts were washed with brine (2 times), dried over Na2SO4, filtered, and concentrated. The residue was purified via column chromatography (ISCO, 330 g silica, 0-15% ethyl acetate/hexanes) to give methyl 3-methyl-7-(methyloxy)-6-(methylthio)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (5.48 g, 82% yield). 1H NMR (400 MHz, DMSO-d6) δ 7.94-8.01 (m, 2H), 7.87 (d, J=7.28 Hz, 1H), 7.77 (d, J=7.53 Hz, 1H), 7.49 (s, 1H), 7.24 (s, 1H), 4.07 (s, 3H), 4.01 (s, 3H), 2.53 (s, 3H), 2.34 (s, 3H); MS (m/z) 422.1 (M+H+).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with methylene chloride (three times)
  3. washThe combined organic extracts were washed with brine (2 times)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified via column chromatography (ISCO, 330 g silica, 0-15% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-30f52a1c18eb45daa4bf63e772009cab
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Linked notes

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