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

HRID 245230ノート

反応式

HRID 245230 の反応式
[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]

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-48b84a8636044bd39231f8b26bfc9bac
出典データセット
uspto-grants-2014_02
特許番号
US08658636B2

反応ノート

読み込み中…