Cesium fluoride → Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoropicolinate

HRID 244319

Reaktionsgleichung

Reaktionsgleichung von HRID 244319
[NH2:1][C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[CH:3]=1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][C:16]=1[F:24].[F-].[Cs+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:18]2[CH:19]=[CH:20][C:15]([Cl:14])=[C:16]([F:24])[CH:17]=2)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[CH:3]=1

Komponenten

5

Edukt 3

HCID 25953Cesium fluorideHCID 27786564-Chloro-3-fluorophenylboronic AcidHCID 86668302Methyl 4-amino-6-chloro-5-fluoropicolinate

Produkt 1

HCID 70498547Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoropicolinateAusbeute 71 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 178418476HCID 178418476, VerbindungKatalysator

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

Methyl 4-amino-6-chloro-5-fluoropicolinate (3.0 g, 14.66 mmol), (4-chloro-3-fluorophenyl)boronic acid (3.07 g, 17.60 mmol), bis(triphenylphosphine)palladium(II) dichloride (1.029 g, 1.466 mmol), and cesium fluoride (4.45 g, 29.3 mmol) were comined in a flask that was sealed and purged with nitrogen. Dioxane (50 ml) and Water (10.00 ml) were added and the reaction mixture was heated at 85° C. for 18 hrs. The reaction mixture was diluted with ethyl acetate and water. The organic phase was washed with saturated sodium chlride, dried over magnesium sulfate, filtered, and concentrated onto silica. The product was purified by flash chromatography (SiO2, 0-40% EtOAc:Hex gradient) to provide the title compound (3.11 g, 10.41 mmol, 71.0% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) d 3.85 (s, 3H), 6.72 (s, 2H), 7.49 (d, J=6.3 Hz, 1H), 7.68-7.80 (m, 2H), 7.84 (dd, J=10.8, 1.3 Hz, 1H); 19F NMR (376 MHz, DMSO-d6) d −144.47, −116.07; ESIMS m/z 299 ([M+H]+).

Aufarbeitung

  1. customthat was sealed
  2. custompurged with nitrogen
  3. additionDioxane (50 ml) and Water (10.00 ml) were added
  4. additionThe reaction mixture was diluted with ethyl acetate and water
  5. washThe organic phase was washed with saturated sodium chlride
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated onto silica
  9. customThe product was purified by flash chromatography (SiO2, 0-40% EtOAc:Hex gradient)

Quellen und Nachweise

ORD-Eintrag
ord-27a9f8f056f84a8891d81a0b5c45f50b
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658568B2

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