Reacción #1596949

Ecuación de reacción

triethylamine

potassium hydrogencarbonate

5-ethyl-2-[3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]tetrahydropyran

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

→

2-{4′-[(3,5-difluoro-4-trifluoromethylphenoxy)difluoromethyl]-2,3′,5′-trifluorobiphenyl-4-yl}-5-ethyltetrahydropyran

Disolventes

water

water

MTBE

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe organic phase is separated off
2. 2
   LavadoThe aqueous phase is washed with MTBE
3. 3
   Lavadothe combined organic phases are washed with saturated sodium chloride solution
4. 4
   Otrodried
5. 5
   ConcentraciónThe solution is concentrated to dryness
6. 6
   Otrothe crude product is purified by column chromatography (SiO2, n-heptane:toluene=1:1)
7. 7
   OtroThe further purification
8. 8
   Otrois carried out by recrystallisation from ethanol and n-heptane

Procedimiento

5.20 g (15.0 mmol) of 5-ethyl-2-[3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]tetrahydropyran are initially introduced in 35 ml of THF together with 6.93 g (15.0 mmol) of 5-((4-bromo-2,6-difluorophenyl)-difluoromethoxy)-1,3-difluoro-2-(trifluoromethyl)benzene. 590 mg (0.75 mmol) of bis(tri-o-tolylphosphine)palladium(II) chloride and 0.1 ml (0.75 mmol) of triethylamine are added. The mixture is heated to 50° C., and a solution of 2.41 g (24.0 mmol) of potassium hydrogencarbonate in 15 ml of water is added. After 3 h at this temperature, water and MTBE are added, and the organic phase is separated off. The aqueous phase is washed with MTBE, and the combined organic phases are washed with saturated sodium chloride solution and dried using sodium sulfate. The solution is concentrated to dryness, and the crude product is purified by column chromatography (SiO2, n-heptane:toluene=1:1). The further purification is carried out by recrystallisation from ethanol and n-heptane, giving 2-{4′-[(3,5-difluoro-4-trifluoromethylphenoxy)difluoromethyl]-2,3′,5′-trifluorobiphenyl-4-yl}-5-ethyltetrahydropyran as a colourless solid having an m.p. of 90° C.

Fuente