Reacción #45746

Ecuación de reacción

potassium fluoride

6-Bromo-4-cyano-7-fluoro-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamide

2,6-di-tert-butylcresol

tributylvinyltin

→

compound

Rendimiento 62.0%

4-Cyano-7-fluoro-N,N,5-trimethyl-6-vinyl-1,3-benzoxazole-2-carboxamide

Rendimiento 62.0%

Disolventes

water

brine

1,4-dioxane

ethyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAfter cooling to room temperature
2. 2
   Otrothe insoluble matter was separated by filtration
3. 3
   Lavadowith washing with ethyl acetate
4. 4
   LavadoThe filtrate was washed with saturated brine
5. 5
   Secadodried over anhydrous sodium sulfate
6. 6
   OtroThe insoluble matter was separated by filtration
7. 7
   Lavadothe organic layer was washed with water
8. 8
   Secadodried over anhydrous sodium sulfate
9. 9
   OtroThe solvent was evaporated away
10. 10
    workup.DISSOLUTIONthe resulting residue was dissolved in tetrahydrofuran (10 ml)
11. 11
    workup.STIRRINGAfter vigorously stirring at the same temperature for 23 hours
12. 12
    Otrothe reaction liquid
13. 13
    ExtracciónThe aqueous layer was further extracted twice with ethyl acetate
14. 14
    Lavadowashed with saturated brine
15. 15
    Secadodried over anhydrous sodium sulfate
16. 16
    OtroThe insoluble matter was separated by filtration
17. 17
    Otrothe solvent was evaporated away
18. 18
    Otrothe resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=3:1)

Procedimiento

6-Bromo-4-cyano-7-fluoro-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamide (I-127) (500 mg, 1.53 mmol), 2,6-di-tert-butylcresol (3 grains) and tetrakis(triphenylphosphine)palladium(0) (177 mg, 0.15 mmol) were dissolved in 1,4-dioxane (10 ml), then at room temperature, tributylvinyltin (601 μl, 1.99 mmol) was added, followed by stirring under nitrogen atmosphere at 100° C. for 17 hours. After cooling to room temperature, the insoluble matter was separated by filtration with washing with ethyl acetate. The filtrate was washed with saturated brine, then dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the organic layer was washed with water, and dried over anhydrous sodium sulfate. The solvent was evaporated away, the resulting residue was dissolved in tetrahydrofuran (10 ml) and water (5 ml), and at room temperature, potassium fluoride (1.782 g, 30.66 mmol) was added. After vigorously stirring at the same temperature for 23 hours, the reaction liquid was fractionated with ethyl acetate and saturated brine. The aqueous layer was further extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, then 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=3:1) to obtain the entitled compound (261 mg, 62%) as a white solid.

Fuente