Methanol → Methyl 6-fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

HRID 245230노트

반응식

HRID 245230 반응식
[F:1][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]([OH:25])=[O:24].[C:26](Cl)(=O)C(Cl)=O.CO>CN(C=O)C.ClCCl>[F:1][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:19])[F:20])[CH:13]=1)[C:6]([CH3:22])=[C:5]2[C:23]([O:25][CH3:26])=[O:24]

참가 물질

6

반응물 3

HCID 887MethanolHCID 65578Oxalyl chlorideHCID 673838086-Fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

생성물 1

HCID 67417240Methyl 6-fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate수율 82.3%

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

DMF (5 drops) was added to a suspension of 6-fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (11.2 g, 32.1 mmol) in dichloromethane (120 mL) at 0° C. Oxalyl chloride (4.21 mL, 48.1 mmol) was added slowly. The mixture was stirred at 0° C. for 1 h. Methanol (30 mL) was added to the mixture, the mixture was stirred at 0° C. for 2 h and warmed to room temperature overnight. The solvent was removed under reduced pressure, and the residue was diluted with water and treated with saturated aqueous NaHCO3 until basic. The aqueous mixture was extracted with methylene chloride (three times). The combined organic phases were washed with brine (two times), dried over Na2SO4, filtered, and concentrated. The residue was purified via column chromatography (ISCO, 120 g Silica, 0-30% ethyl acetate/hexanes) to give methyl 6-fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (9.6 g, 82% yield). MS (m/z) 364.1 (M+H+).

후처리

  1. stirringthe mixture was stirred at 0° C. for 2 h
  2. temperaturewarmed to room temperature overnight
  3. customThe solvent was removed under reduced pressure
  4. additionthe residue was diluted with water
  5. additiontreated with saturated aqueous NaHCO3 until basic
  6. extractionThe aqueous mixture was extracted with methylene chloride (three times)
  7. washThe combined organic phases were washed with brine (two times)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified via column chromatography (ISCO, 120 g Silica, 0-30% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-48b84a8636044bd39231f8b26bfc9bac
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658636B2

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