Toluene → 3-(3-Chloro-2-fluoro-phenylamino)-3-phenyl-acrylic acid ethyl ester

HRID 244225

반응식

HRID 244225 반응식
[F:1][C:2]1[C:8]([Cl:9])=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[C:10]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])(=O)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>C(Cl)Cl.O>[CH2:22]([O:21][C:19](=[O:20])[CH:18]=[C:10]([NH:4][C:3]1[CH:5]=[CH:6][CH:7]=[C:8]([Cl:9])[C:2]=1[F:1])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:23]

참가 물질

7

반응물 4

HCID 1140TolueneHCID 6101p-Toluenesulfonic acidHCID 7170Ethyl benzoylacetateHCID 750143-Chloro-2-fluoroaniline

생성물 1

HCID 666763623-(3-Chloro-2-fluoro-phenylamino)-3-phenyl-acrylic acid ethyl ester

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

2-Fluoro-3-chloroaniline (7.55 mL, 0.0687 mole), ethyl benzoylacetate (13.2 g, 0.0687 mole) and p-toluenesulfonic acid (1.18 g, 0.007 mole) were combined in a 250 mL round bottom flask with toluene (60 mL) and a magnetic stir-bar. The reaction was stirred at reflux with a Dean-Stark water trap. Reflux was stopped after 3 h. The product mixture was allowed to cool, and was then passed through a short pad of silica gel with methylene chloride, and concentrated in vacuo. Standing under high vacuum for 1 h afforded an oil. The oil was stirred in 100 mL of hexanes overnight, then suction filtered to remove a solid impurity. The filtrate was concentrated, and put on high vacuum to afford an oil. The oil was chromatographed with hexanes, ethyl acetate (8:1), and put under high vacuum for 1 h to afford the title compound as a yellow oil; 1H NMR (CDCl3, 400 MHz) δ 1.30-1.34 (t, 3H, J=7.1 Hz), 4.20-4.25 (Q, 2H, J=7.1 Hz), 5.13 (s, 1H), 6.19-6.23 (t, 1H), 6.60-6.65 (t of d, 1H, J=1.7 & J=8.2), 6.88-6.92 (t of d, 1H, J=1.5 & J=6.6), 7.29-7.37 (m, 5H), 10.21 (bs, 1H); MS (ES+): 319.99 (100) [MH+], 322.02 (30) [(M+2)H+].

후처리

  1. temperatureReflux
  2. temperatureto cool
  3. concentrationconcentrated in vacuo
  4. waitStanding under high vacuum for 1 h
  5. customafforded an oil
  6. filtrationsuction filtered
  7. customto remove a solid impurity
  8. concentrationThe filtrate was concentrated
  9. customto afford an oil
  10. customThe oil was chromatographed with hexanes, ethyl acetate (8:1)
  11. waitput under high vacuum for 1 h

출처 및 근거

ORD 기록
ord-4465367071bd459cb9765df57d6bae87
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08653268B2

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