반응 #1596949

반응 방정식

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

용매

water

water

MTBE

THF

반응 조건

후처리

1. 1
   기타the organic phase is separated off
2. 2
   세척The aqueous phase is washed with MTBE
3. 3
   세척the combined organic phases are washed with saturated sodium chloride solution
4. 4
   기타dried
5. 5
   농축The solution is concentrated to dryness
6. 6
   기타the crude product is purified by column chromatography (SiO2, n-heptane:toluene=1:1)
7. 7
   기타The further purification
8. 8
   기타is carried out by recrystallisation from ethanol and n-heptane

실험 절차

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.

출처