Water → Ethyl 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate

HRID 246963Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246963
[CH3:1]N(C)C=O.P(Cl)(Cl)(Cl)=O.[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[NH:19][C:20]1[N:33]=C(OC)[C:31]([F:36])=[CH:30][C:21]=1[C:22]([CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])=[O:23].O.[CH:38]([Cl:41])(Cl)Cl>ClCCCl>[Cl:41][C:38]1[N:33]=[C:20]2[C:21]([C:22](=[O:23])[C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:1][N:19]2[C:13]2[CH:14]=[CH:15][C:16]([F:18])=[CH:17][C:12]=2[F:11])=[CH:30][C:31]=1[F:36]

Komponenten

7

Edukt 5

HCID 962WaterHCID 6212ChloroformHCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 15596920Ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinoyl]acetate

Produkt 1

HCID 1268243Ethyl 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylateAusbeute 62,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 111,2-DichloroethaneLösungsmittel

Versuchsvorschrift

In 2 ml of 1,2-dichloroethane was dissolved 130 mg of N,N-dimethylformamide, and 270 mg of phosphorus oxychloride was dropped thereinto with ice-cooling, after which the resulting mixture was subjected to reaction at the same temperature for 10 minutes. Thereafter, 200 mg of ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinoyl]acetate was added to the reaction mixture, and the resulting mixture was subjected to reaction under reflux for 4.5 hours. The reaction mixture was poured into 30 ml of water, and 30 ml of chloroform was then added thereto. The organic layer was thereafter separated, washed successively with 20 ml of water and 20 ml of saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and the residue thus obtained was purified by a column chromatography [Wako Silica Gel C-200, eluant: benzene-ethyl acetate (10:1 by volume)] to obtain 130 mg (yield 62.6%) of ethyl 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate. The physical properties of this compound were identical with those of the compound obtained in Example 51.

Aufarbeitung

  1. additionwas dropped
  2. temperaturewith ice-cooling
  3. customafter which the resulting mixture was subjected to reaction at the same temperature for 10 minutes
  4. customthe resulting mixture was subjected to reaction
  5. temperatureunder reflux for 4.5 hours
  6. additionwas then added
  7. customThe organic layer was thereafter separated
  8. washwashed successively with 20 ml of water and 20 ml of saturated aqueous sodium chloride solution
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solvent was removed by distillation under reduced pressure
  11. customthe residue thus obtained
  12. customwas purified by a column chromatography [Wako Silica Gel C-200, eluant: benzene-ethyl acetate (10:1 by volume)]

Quellen und Nachweise

ORD-Eintrag
ord-f5ec162a79fc4c25a0a716380dafba75
Quelldatensatz
uspto-grants-1987_11
Patentnummer
US04704459

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