Potassium Phosphate, Tribasic → 5-(3,5-Difluorophenyl)-2,3-difluoropyridine

HRID 40313

Reaktionsgleichung

Reaktionsgleichung von HRID 40313
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:9][C:10]1[CH:11]=[C:12](B(O)O)[CH:13]=[C:14]([F:16])[CH:15]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Cl[C:55]1[CH:56]=[C:57]([F:62])[C:58]([F:61])=[N:59][CH:60]=1>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:9][C:10]1[CH:11]=[C:12]([C:55]2[CH:56]=[C:57]([F:62])[C:58]([F:61])=[N:59][CH:60]=2)[CH:13]=[C:14]([F:16])[CH:15]=1

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 27832485-Chloro-2,3-difluoropyridineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl

Produkt 1

HCID 675027115-(3,5-Difluorophenyl)-2,3-difluoropyridine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of palladium (II) acetate (0.0375 g, 0.167 mmol), potassium phosphate (2.13 g, 10.0 mmol), 3,5-difluorophenylboronic acid (1.58 g, 10.0 mmol), X-Phos (0.159 g, 0.334 mmol) and 5-chloro-2,3-difluoropyridine (0.347 ml, 3.34 mmol) was diluted with 1,4-dioxane (0.1M, 33.4 mL) and water (0.3M, 11.0 mL) and was heated under nitrogen at 100° C. for 45 minutes. The reaction was concentrated in vacuo. The concentrated material was triturated with water, filtered and rinsed with MeCN. The crude solid was taken up in dichloromethane and filtered over a plug of Celite to eliminate residual palladium. The material was dissolved in minimal DCM, and purified via MPLC (eluting with 0-10% EtOAc in hexanes) to yield 5-(3,5-difluorophenyl)-2,3-difluoropyridine. The material was converted to the hydrazine in a method similar to that in the synthesis of (S)-6-(1-(8-fluoro-6-(3-methylisothiazol-5-yl)-[1,2,4]triazolo[4,3-α]pyridin-3-yl)ethyl)quinoline.

Aufarbeitung

  1. concentrationThe reaction was concentrated in vacuo
  2. customThe concentrated material was triturated with water
  3. filtrationfiltered
  4. washrinsed with MeCN
  5. filtrationfiltered over a plug of Celite
  6. dissolutionThe material was dissolved in minimal DCM
  7. custompurified via MPLC (eluting with 0-10% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-f8a17af4ee534c619b8a9a42877539c8
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524900B2

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