Cesium fluoride → 4-Acetylamino-3-chloro-6-(2-fluoro-3-methoxy-4-trifluoromethylphenyl)pyridine-2-carboxylic acid methyl ester

HRID 1782617

Reaktionsgleichung

Reaktionsgleichung von HRID 1782617
[CH3:1][O:2][C:3]([C:5]1[C:10]([Cl:11])=[C:9]([NH:12][C:13](=[O:15])[CH3:14])[CH:8]=[C:7](Cl)[N:6]=1)=[O:4].[F:17][C:18]1[C:23]([O:24][CH3:25])=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=[CH:20][C:19]=1[Sn](C)(C)C.[F-].[Cs+].C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3]([C:5]1[C:10]([Cl:11])=[C:9]([NH:12][C:13](=[O:15])[CH3:14])[CH:8]=[C:7]([C:19]2[CH:20]=[CH:21][C:22]([C:26]([F:28])([F:29])[F:27])=[C:23]([O:24][CH3:25])[C:18]=2[F:17])[N:6]=1)=[O:4]

Komponenten

7

Edukt 4

HCID 25953Cesium fluorideHCID 821241,4-Bis(diphenylphosphino)butaneHCID 22677481Methyl 4-acetamido-3,6-dichloropyridine-2-carboxylateHCID 68810358(2-Fluoro-3-methoxy-4-trifluoromethylphenyl)trimethyl stannane

Produkt 1

HCID 688110344-Acetylamino-3-chloro-6-(2-fluoro-3-methoxy-4-trifluoromethylphenyl)pyridine-2-carboxylic acid methyl esterAusbeute 10 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

In an oven dried, nitrogen flushed 100 mL 3 neck flask equipped with a condenser and a magnetic stirbar was dissolved methyl-4-acetamido-3,6-dichloropyridine-2-carboxylate (1.2 g, 4.6 mmol) and (2-fluoro-3-methoxy-4-trifluoromethylphenyl)trimethyl stannane (1.7 g, 4.6 mmol) in acetonitrile (15 mL) and the resulting solution was de-aerated with a purge of nitrogen for 15 minutes. Cesium fluoride (2.1 g, 13.9 mmol), 1,4-bis(diphenylphosphino)butane (0.2 g, 0.46 mmol) and palladium acetate (0.1 g, 0.46 mmol) were added and the head space of the reaction was purged with nitrogen as the reaction was heated to reflux with stirring. The reaction was then stirred under an open nitrogen atmosphere for 5 hours by which time TLC (hexane:ethyl acetate/1:2) indicated complete consumption of starting material. The cooled reaction was filtered through celite with ethyl acetate and the filtrate concentrated and purified by flash silica gel chromatography (hexanes:ethyl acetate/2:1) to give 4-acetylamino-3-chloro-6-(2-fluoro-3-methoxy-4-trifluoromethylphenyl)pyridine-2-carboxylic acid methyl ester (0.19 g, 0.46 mmol) as an oil: 1H NMR (CDCl3): δ 9.03 (d, 1H), 8.02 (bs, 1H), 7.68 (bt, 1H), 7.42 (bd, 1H), 4.03 (d, 3H), 4.01 (s, 3H), 2.33 (s, 3H).

Aufarbeitung

  1. customIn an oven dried
  2. customnitrogen flushed 100 mL 3 neck flask
  3. customequipped with a condenser
  4. customa purge of nitrogen for 15 minutes
  5. customthe head space of the reaction was purged with nitrogen as the reaction
  6. temperaturewas heated
  7. temperatureto reflux
  8. stirringThe reaction was then stirred under an open nitrogen atmosphere for 5 hours by which time TLC (hexane:ethyl acetate/1:2)
  9. customconsumption of starting material
  10. customThe cooled reaction
  11. filtrationwas filtered through celite with ethyl acetate
  12. concentrationthe filtrate concentrated
  13. custompurified by flash silica gel chromatography (hexanes:ethyl acetate/2:1)

Quellen und Nachweise

ORD-Eintrag
ord-ef88bfceac19452d82b5de6467be35e3
Quelldatensatz
uspto-grants-2009_03
Patentnummer
US07498468B2

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