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

HRID 245201ノート

反応式

HRID 245201 の反応式
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[C:7]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=1)[C:6]([CH3:24])=[C:5]2[C:25]([OH:27])=[O:26].[C:28](Cl)(=O)C(Cl)=O.CO>CN(C=O)C.ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[C:7]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:21])[F:22])[CH:15]=1)[C:6]([CH3:24])=[C:5]2[C:25]([O:27][CH3:28])=[O:26]

参加物

6

反応物 3

HCID 887MethanolHCID 65578Oxalyl chlorideHCID 673838286-Bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

生成物 1

HCID 67384067Methyl 6-bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate収率 68%

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-bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (42.6 g, 97 mmol) in dichloromethane (500 mL) at 0° C. Oxalyl chloride (12.71 mL, 145 mmol) was added slowly. The mixture was stirred at 0° C. for 1 h. MeOH (30 mL) was added, and the resulting mixture was stirred at 0° C. for 2 h and allowed to warm to room temperature overnight. The solvent was removed under reduced pressure. The residue was diluted with water, treated with saturated aqueous NaHCO3, and extracted with methylene chloride. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified via column chromatography (ISCO, 330 g silica, 40-100% methylene chloride/hexanes) to afford methyl 6-bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (29.8 g, 68% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.05 (s, 1H), 7.96-8.01 (m, 2H), 7.89 (d, J=7.78 Hz, 1H), 7.77 (t, J=7.65 Hz, 1H), 7.65 (s, 1H), 4.08 (s, 3H), 4.03 (s, 3H), 2.34 (s, 3H); MS (m/z) 455.0 (M+H+).

後処理

  1. stirringthe resulting mixture was stirred at 0° C. for 2 h
  2. temperatureto warm 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
  6. extractionextracted with methylene chloride
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude material was purified via column chromatography (ISCO, 330 g silica, 40-100% methylene chloride/hexanes)

出典と根拠

ORDレコード
ord-5e139e52441743968d98fa9411249d93
出典データセット
uspto-grants-2014_02
特許番号
US08658636B2

反応ノート

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