Reaktion #45729

Reaktionsgleichung

ammonium chloride

6-Bromo-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile

3,5-difluorophenylboronic acid

tripotassium phosphate

→

2-Cyclopropyl-6-(3,5-difluorophenyl)-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile

Lösungsmittel

1,4-dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to room temperature
2. 2
   workup.STIRRINGby stirring at room temperature for 5 minutes
3. 3
   ExtraktionThis was extracted twice with ethyl acetate
4. 4
   Waschenwashed with saturated brine
5. 5
   Trocknendried over anhydrous sodium sulfate
6. 6
   SonstigeThe insoluble matter was separated by filtration
7. 7
   Sonstigethe solvent was evaporated away
8. 8
   Sonstigethe resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=8:1)
9. 9
   Sonstigeto obtain
10. 10
    workup.ADDITIONthe entitled compound (240.5 mg containing impurities (reference)) as a white solid
11. 11
    Sonstigeto separate
12. 12
    Sonstigethey are separated in the next step

Vorschrift

6-Bromo-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-77) (200 mg, 0.68 mmol), 3,5-difluorophenylboronic acid (428 mg, 2.71 mmol) and tripotassium phosphate (288 mg, 1.36 mmol) were dissolved in 1,4-dioxane (8 ml), then at room temperature, tetrakis(triphenylphosphine)palladium(0) (157 mg, 0.14 mmol) was added. The solution was stirred under nitrogen atmosphere at 95° C. for 60 hours. After cooling to room temperature, aqueous saturated ammonium chloride solution was added to the reaction liquid, followed by stirring at room temperature for 5 minutes. This was extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away, and the resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=8:1) to obtain the entitled compound (240.5 mg containing impurities (reference)) as a white solid. Since the impurities were difficult to separate, they are separated in the next step.

Quelle