1,4-Dioxane → HCID 86695924, Verbindung

HRID 870931Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 870931
Cl[C:2]1[C:7]([C:8]([O-:10])=[O:9])=[CH:6][N:5]=[CH:4][C:3]=1[F:11].[Cl:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[C:15]([F:22])[CH:14]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOC[CH2:32]1>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:2]2[C:7]([C:8]([O:10][CH3:32])=[O:9])=[CH:6][N:5]=[CH:4][C:3]=2[F:11])=[C:15]([F:22])[CH:14]=1

Komponenten

7

Edukt 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 4193595(4-Chloro-2-fluorophenyl)boronic acidHCID 86335698HCID 86335698, Verbindung

Produkt 1

HCID 86695924HCID 86695924, VerbindungAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of 4-chloro-5-fluoronicotinate (1.2 g, 6.33 mmol) in 1,4-dioxane (12 mL) and water (0.5 mL) was added (4-chloro-2-fluorophenyl)boronic acid (1.214 g, 6.96 mmol) and potassium phosphate, dibasic (2.205 g, 12.66 mmol). To this mixture, PdCl2(dppf) (0.371 g, 0.506 mmol) was added and the solution purged with N2 for 10 min then heated to 80° C. for 12 h. The mixture was cooled to room temperature and water (25 mL) was added. The solution was extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine (25 mL) and concentrated under reduced pressure to afford the residue which was purified by silica gel column using a gradient of ethyl acetate in hexanes to afford methyl 4-(4-chloro-2-fluorophenyl)-5-fluoronicotinate (900 mg, 3.17 mmol, 50% yield) as a yellow solid. LCMS (ESI) m/e 284.0 [(M+H)+, calcd for C13H9ClF2NO2 284.0]; LC/MS retention time (Method F): tR=1.01 min.

Aufarbeitung

  1. customthe solution purged with N2 for 10 min
  2. temperatureThe mixture was cooled to room temperature
  3. additionwater (25 mL) was added
  4. extractionThe solution was extracted with ethyl acetate (3×25 mL)
  5. washThe combined organic layers were washed with brine (25 mL)
  6. concentrationconcentrated under reduced pressure
  7. customto afford the residue which
  8. customwas purified by silica gel column

Quellen und Nachweise

ORD-Eintrag
ord-8e74e5d14c3a456d99b6dd438aafd92c
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969564B2

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