Reaction #1596949

Reaction equation

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

Solvents

water

water

MTBE

THF

Conditions

Workup

1. 1
   Otherthe organic phase is separated off
2. 2
   WashThe aqueous phase is washed with MTBE
3. 3
   Washthe combined organic phases are washed with saturated sodium chloride solution
4. 4
   Otherdried
5. 5
   ConcentrationThe solution is concentrated to dryness
6. 6
   Otherthe crude product is purified by column chromatography (SiO2, n-heptane:toluene=1:1)
7. 7
   OtherThe further purification
8. 8
   Otheris carried out by recrystallisation from ethanol and n-heptane

Procedure

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.

Source