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

HRID 245181

반응식

HRID 245181 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 3283Diethyl Ether용매

반응 조건

온도
100 °C

실험 절차

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+).

후처리

  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)

출처 및 근거

ORD 기록
ord-30f52a1c18eb45daa4bf63e772009cab
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658636B2

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