Reacción #1596951

Ecuación de reacción

4-(4-ethylcyclohexyl)-2-fluorobenzeneboronic acid

hydrazine hydroxide

5-((4-bromo-2,6-difluorophenyl)difluoromethoxy)-1,3-difluoro-2-(trifluoromethyl)benzene

sodium metaborate

→

4-[(3,5-difluoro-4-trifluoromethylphenoxy)difluoromethyl]-4′-(4-ethylcyclohexyl)-3,5,2′-trifluorobiphenyl

Disolventes

water

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroat room temperature
2. 2
   Temperaturathe mixture is heated at the boil for 18 h
3. 3
   TemperaturaAfter cooling
4. 4
   Extracciónthe batch is extracted with MTBE
5. 5
   ExtracciónThe aqueous phase is extracted with MTBE
6. 6
   Lavadothe combined organic phases are washed with water and saturated sodium chloride solution
7. 7
   OtroThe solution is dried
8. 8
   Concentraciónconcentrated to dryness
9. 9
   OtroThe crude product is purified by column chromatography (SiO2, n-heptane:1-chlorobutane=9:1)
10. 10
    OtroThe further purification
11. 11
    Otrois carried out by recrystallisation from ethanol and n-heptane

Procedimiento

0.11 ml (2.33 mmol) of hydrazine hydroxide is added to a mixture of 9.70 g (22.1 mmol) of 5-((4-bromo-2,6-difluorophenyl)difluoromethoxy)-1,3-difluoro-2-(trifluoromethyl)benzene, 12 ml (18 mmol) of 1.5 N aqueous sodium metaborate soln. and 0.62 g (0.88 mmol) of bis(triphenylphosphine)palladium(II) chloride in 150 ml of THF at room temperature. 6.1 g (24.3 mmol) of 4-(4-ethylcyclohexyl)-2-fluorobenzeneboronic acid are added, and the mixture is heated at the boil for 18 h. After cooling, water is added, and the batch is extracted with MTBE. The aqueous phase is extracted with MTBE, and the combined organic phases are washed with water and saturated sodium chloride solution. The solution is dried using sodium sulfate and concentrated to dryness. The crude product is purified by column chromatography (SiO2, n-heptane:1-chlorobutane=9:1). The further purification is carried out by recrystallisation from ethanol and n-heptane, giving 4-[(3,5-difluoro-4-trifluoromethylphenoxy)difluoromethyl]-4′-(4-ethylcyclohexyl)-3,5,2′-trifluorobiphenyl as a colourless solid having an m.p. of 77° C.

Fuente