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

HRID 245181

反応式

HRID 245181 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 3283Diethyl Ether溶媒

反応条件

温度
100 °C

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-30f52a1c18eb45daa4bf63e772009cab
出典データセット
uspto-grants-2014_02
特許番号
US08658636B2

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