반응 #45729

반응 방정식

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

용매

1,4-dioxane

반응 조건

후처리

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

실험 절차

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.

출처