Реакция #1596951

Уравнение реакции

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

Растворители

water

THF

Условия реакции

Обработка

1. 1
   Другоеat room temperature
2. 2
   Температураthe mixture is heated at the boil for 18 h
3. 3
   ТемператураAfter cooling
4. 4
   Экстракцияthe batch is extracted with MTBE
5. 5
   ЭкстракцияThe aqueous phase is extracted with MTBE
6. 6
   Промывкаthe combined organic phases are washed with water and saturated sodium chloride solution
7. 7
   ДругоеThe solution is dried
8. 8
   Концентрированиеconcentrated to dryness
9. 9
   ДругоеThe crude product is purified by column chromatography (SiO2, n-heptane:1-chlorobutane=9:1)
10. 10
    ДругоеThe further purification
11. 11
    Другоеis carried out by recrystallisation from ethanol and n-heptane

Методика

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.

Источник