Reaktion #45724

Reaktionsgleichung

ammonium chloride

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

phenylboronic acid

tripotassium phosphate

→

compound

Ausbeute 92.2%

2-Cyclopropyl-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

Ausbeute 92.2%

Lösungsmittel

1,4-dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to room temperature
2. 2
   workup.STIRRINGby stirring at room temperature for 10 minutes
3. 3
   SonstigeThe insoluble matter was separated by filtration
4. 4
   Waschenwith washing with ethyl acetate
5. 5
   Extraktionfurther the aqueous layer of the filtrate was extracted twice with ethyl acetate
6. 6
   Waschenwashed with saturated brine
7. 7
   Trocknendried over anhydrous sodium sulfate
8. 8
   SonstigeThe insoluble matter was separated by filtration
9. 9
   Sonstigethe solvent was evaporated away
10. 10
    Sonstigethe resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=8:1)

Vorschrift

6-Bromo-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-77) (300 mg, 1.02 mmol), phenylboronic acid (256 mg, 2.03 mmol) and tripotassium phosphate (432 mg, 2.03 mmol) were dissolved in 1,4-dioxane (6 ml), then tetrakis(triphenylphosphine)palladium(0) (118 mg, 0.10 mmol) was added at room temperature. The solution was stirred under nitrogen atmosphere at 100° C. for 17 hours. After cooling to room temperature, aqueous saturated ammonium chloride solution was added to the reaction liquid, followed by stirring at room temperature for 10 minutes. The insoluble matter was separated by filtration with washing with ethyl acetate, and further the aqueous layer of the filtrate 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 (275 mg, 92%) as a white solid.

Quelle