Acetic Acid → 7-[(4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid ethyl ester

HRID 51966

Reaktionsgleichung

Reaktionsgleichung von HRID 51966
[NH2:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]([C:13]2[C:14]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:12])[CH:5]=[CH:6][C:7]=1C=O.[CH2:29]([O:31][C:32](=[O:36])[CH:33]=[CH:34]O)[CH3:30].[Na].[C:38](O)(=O)C>>[CH2:29]([O:31][C:32]([C:33]1[CH:38]=[N:1][C:2]2[C:7]([CH:34]=1)=[CH:6][CH:5]=[C:4]([NH:10][C:11]([C:13]1[C:14]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:27])([F:26])[F:28])=[CH:21][CH:20]=3)=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:12])[CH:3]=2)=[O:36])[CH3:30]

Komponenten

5

Edukt 4

HCID 176Acetic AcidHCID 428818beta-Hydroxyacrylic acid ethyl ester3×HCID 5360545Sodium3×HCID 101346044'-Trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-4-formyl-phenyl)-amide

Produkt 1

HCID 101832717-[(4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid ethyl ester

Versuchsvorschrift

A solution of 4′-trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-4-formyl-phenyl)-amide (7 g, 18.2 mmol, 1 equiv) and 3-hydroxy-acrylic acid ethyl ester, sodium salt (2.52 g, 18.2 mmol, 1 equiv) in glacial acetic acid (70 mL, 10 volumes) was heated at 80° C. for 2 hours. Additional 3-hydroxy-acrylic acid ethyl ester, sodium salt (2.52 g, 18.2 mmol, 1 equiv) was added and the solution heated for 15 hours. Again, additional 3-hydroxy-acrylic acid ethyl ester, sodium salt (1.26 g, 9.1 mmol, 0.5 equiv) was added and the solution heated for another 4 hours. The reaction mixture was concentrated in vacuo. The residue was dissolved in EtOAc (300 mL) and the organic layer was washed with a saturated aqueous sodium carbonate solution (2×200 mL) and 1 N NaOH solution (200 mL). The combined aqueous layers were back extracted with ethyl acetate (200 mL). The combined organic layers were dried over sodium sulfate and treated with Darco G-60® (7 g). The solids were removed by filtration and the filtrate was concentrated to afford crude 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid ethyl ester, which was used in the next step without further purification.

Aufarbeitung

  1. temperaturethe solution heated for 15 hours
  2. temperaturethe solution heated for another 4 hours
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. dissolutionThe residue was dissolved in EtOAc (300 mL)
  5. washthe organic layer was washed with a saturated aqueous sodium carbonate solution (2×200 mL) and 1 N NaOH solution (200 mL)
  6. extractionThe combined aqueous layers were back extracted with ethyl acetate (200 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. additiontreated with Darco G-60® (7 g)
  9. customThe solids were removed by filtration
  10. concentrationthe filtrate was concentrated

Quellen und Nachweise

ORD-Eintrag
ord-73b17bf7c0474960b51461ff373804ab
Quelldatensatz
uspto-grants-2004_03
Patentnummer
US06713489B2

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