Reacción #45729

Ecuación de reacción

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

Disolventes

1,4-dioxane

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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.

Fuente