Réaction #1596951

Équation de réaction

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

Solvants

water

THF

Conditions de réaction

Traitement

1. 1
   Autreat room temperature
2. 2
   Températurethe mixture is heated at the boil for 18 h
3. 3
   TempératureAfter cooling
4. 4
   Extractionthe batch is extracted with MTBE
5. 5
   ExtractionThe aqueous phase is extracted with MTBE
6. 6
   Lavagethe combined organic phases are washed with water and saturated sodium chloride solution
7. 7
   AutreThe solution is dried
8. 8
   Concentrationconcentrated to dryness
9. 9
   AutreThe crude product is purified by column chromatography (SiO2, n-heptane:1-chlorobutane=9:1)
10. 10
    AutreThe further purification
11. 11
    Autreis carried out by recrystallisation from ethanol and n-heptane

Mode opératoire

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.

Source