Water → Ethyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl](ethoxy)acetate

HRID 56822

Reaktionsgleichung

Reaktionsgleichung von HRID 56822
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]2[C:15]([O:16][CH3:17])=[CH:14][NH:13][C:12](=[O:18])[CH:11]=2)[CH:3]=1.[H-].[Na+].Cl[CH:22]([O:28][CH2:29][CH3:30])[C:23]([O:25][CH2:26][CH3:27])=[O:24].O>CN(C)C=O>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]2[C:15]([O:16][CH3:17])=[CH:14][N:13]([CH:22]([O:28][CH2:29][CH3:30])[C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:12](=[O:18])[CH:11]=2)[CH:3]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 24758Sodium hydrideHCID 2724873Ethyl 2-chloro-2-ethoxyacetateHCID 1176049354-Chloro-2-(5-methoxy-2-oxo-1,2-dihydropyridin-4-yl)benzonitrile3×

Produkt 1

HCID 117622855Ethyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl](ethoxy)acetate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Under argon and at 0° C., 10 min apart two portions of in total 350 mg (purity 82%, 1.10 mmol) of 4-chloro-2-(5-methoxy-2-oxo-1,2-dihydropyridin-4-yl)benzonitrile were added to a suspension of 53 mg (1.32 mmol, 1.2 eq.) of sodium hydride (60% in mineral oil) in 2.1 ml of dimethylformamide. The reaction mixture was stirred at RT for 60 min and then cooled back to 0° C., 245 mg (purity 90%, 1.32 mmol, 1.2 eq.) of ethyl 2-chloro-2-ethoxyacetate were added and the mixture was stirred at RT for 2 h. This batch together with an analogous test batch was combined with 50 mg (purity 82%, 0.16 mmol) of 4-chloro-2-(5-methoxy-2-oxo-1,2-dihydropyridin-4-yl)benzonitrile. After addition of 20 ml of water and phase separation, the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried (sodium sulphate), filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (IR-50Si, petroleum ether/ethyl acetate 15-50%). Yield: 277 mg (55% of theory based on in total 1.26 mmol of 4-chloro-2-(5-methoxy-2-oxo-1,2-dihydropyridin-4-yl)benzonitrile employed)

Aufarbeitung

  1. temperaturecooled back to 0° C.
  2. stirringthe mixture was stirred at RT for 2 h
  3. extractionthe aqueous phase was extracted twice with ethyl acetate
  4. dry with materialThe combined organic phases were dried (sodium sulphate)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by flash chromatography (IR-50Si, petroleum ether/ethyl acetate 15-50%)

Quellen und Nachweise

ORD-Eintrag
ord-068ff5cad5eb425f90d422c004891aa9
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434690B2

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