Sodium metaborate → 4-[(3,5-Difluoro-4-trifluoromethylphenoxy)difluoromethyl]-4'-(4-ethylcyclohexyl)-3,5,2'-trifluorobiphenyl

HRID 1509769Notes

Reaction equation

HRID 1509769 reaction equation
[OH-].NN.Br[C:5]1[CH:10]=[C:9]([F:11])[C:8]([C:12]([F:27])([F:26])[O:13][C:14]2[CH:15]=[C:16]([F:25])[C:17]([C:21]([F:24])([F:23])[F:22])=[C:18]([F:20])[CH:19]=2)=[C:7]([F:28])[CH:6]=1.B([O-])=O.[Na+].[CH2:33]([CH:35]1[CH2:40][CH2:39][CH:38]([C:41]2[CH:46]=[CH:45][C:44](B(O)O)=[C:43]([F:50])[CH:42]=2)[CH2:37][CH2:36]1)[CH3:34]>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[F:20][C:18]1[CH:19]=[C:14]([CH:15]=[C:16]([F:25])[C:17]=1[C:21]([F:24])([F:23])[F:22])[O:13][C:12]([F:27])([F:26])[C:8]1[C:9]([F:11])=[CH:10][C:5]([C:44]2[CH:45]=[CH:46][C:41]([CH:38]3[CH2:37][CH2:36][CH:35]([CH2:33][CH3:34])[CH2:40][CH2:39]3)=[CH:42][C:43]=2[F:50])=[CH:6][C:7]=1[F:28]

Participants

8

Reactant 4

HCID 145326Sodium metaborateHCID 22602656CID 22602656HCID 58444567HCID 58444567, compoundHCID 584445914-(4-Ethylcyclohexyl)-2-fluorophenylboronic acid

Product 1

HCID 584445854-[(3,5-Difluoro-4-trifluoromethylphenoxy)difluoromethyl]-4'-(4-ethylcyclohexyl)-3,5,2'-trifluorobiphenyl

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  1. customat room temperature
  2. temperaturethe mixture is heated at the boil for 18 h
  3. temperatureAfter cooling
  4. extractionthe batch is extracted with MTBE
  5. extractionThe aqueous phase is extracted with MTBE
  6. washthe combined organic phases are washed with water and saturated sodium chloride solution
  7. customThe solution is dried
  8. concentrationconcentrated to dryness
  9. customThe crude product is purified by column chromatography (SiO2, n-heptane:1-chlorobutane=9:1)
  10. customThe further purification
  11. customis carried out by recrystallisation from ethanol and n-heptane

Sources & evidence

ORD record
ord-a863bf41bcca43c5804a8746830b960f
Source dataset
uspto-grants-2012_07
Patent number
US08211513B2

Reaction notes

Loading…