Reaction #1596946

Reaction equation

2-fluoro-4-(trans-5-propyltetrahydropyran-2-yl)phenyl trifluoromethanesulfonate

2-{4-[(3,5-difluoro-4-trifluoromethylphenoxy)difluoromethyl]-3,5-difluorophenyl}-4,4,5,5-tetramethyl-1,3,2-dioxaborolan

sodium carbonate

→

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

Solvents

toluene ethanol

Conditions

Workup

1. 1
   Temperatureis heated
2. 2
   Temperatureunder reflux for 20 h
3. 3
   TemperatureAfter cooling
4. 4
   Otherthe organic phase is separated off
5. 5
   Extractionthe aqueous phase is extracted with MTBE
6. 6
   WashThe combined organic phases are washed with water
7. 7
   OtherThe solution is dried
8. 8
   Concentrationconcentrated to dryness
9. 9
   OtherThe residue is purified by column chromatography (SiO2, n-heptane:toluene=7:3)
10. 10
    OtherThe further purification
11. 11
    Otheris carried out by recrystallisation from ethanol and n-heptane

Procedure

A mixture of 10.0 g (27.0 mmol) of 2-fluoro-4-(trans-5-propyltetrahydropyran-2-yl)phenyl trifluoromethanesulfonate and 14.3 g (29.4 mmol) of 2-{4-[(3,5-difluoro-4-trifluoromethylphenoxy)difluoromethyl]-3,5-difluorophenyl}-4,4,5,5-tetramethyl-1,3,2-dioxaborolan, 1.50 g (1.30 mmol) of tetrakis(triphenylphosphine)palladium(0) and 30 ml of 2 N sodium carbonate solution in 100 ml of toluene/ethanol (1:1) is heated under reflux for 20 h. After cooling, the organic phase is separated off, and the aqueous phase is extracted with MTBE. The combined organic phases are washed with water. The solution is dried using sodium sulfate and concentrated to dryness. The residue is purified by column chromatography (SiO2, n-heptane:toluene=7:3). 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-propyltetrahydropyran as a colourless solid (m.p. 95° C.).

Source