Diethyl Ether → HCID 88929386, compound

HRID 1429279Notes

Reaction equation

HRID 1429279 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[C:4]([F:12])[CH:3]=1.C(OCC)C.C([Li])CCC.[F:23][C:24]1[CH:29]=[C:28]([CH:30]2[CH2:35][CH2:34][CH:33]([CH2:36][CH2:37][CH3:38])[CH2:32][CH2:31]2)[CH:27]=[CH:26][C:25]=1[C:39]([F:43])=[C:40](F)[F:41]>C1(C)C=CC=CC=1>[F:43]/[C:39](/[C:25]1[CH:26]=[CH:27][C:28]([CH:30]2[CH2:35][CH2:34][CH:33]([CH2:36][CH2:37][CH3:38])[CH2:32][CH2:31]2)=[CH:29][C:24]=1[F:23])=[C:40](/[F:41])\[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[C:4]([F:12])[CH:3]=1

Participants

6

Reactant 4

HCID 3283Diethyl Ether2×HCID 27829044-Bromo-2-fluorobenzotrifluorideHCID 68304419HCID 68304419, compoundHCID 178418339Butyllithium

Product 1

HCID 88929386HCID 88929386, compoundYield 56.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a reaction vessel under a nitrogen atmosphere, 4-bromo-2-fluoro-1-(trifluoromethyl)benzene (2.28 g) and diethyl ether (70 ml) were added, and cooling was carried out to −70° C. Thereto, a n-butyllithium (1.57 M) n-hexane solution (7.10 ml) was added dropwise in a temperature range of −70° C. to −65° C., and stirring was carried out for another 1 hour. Subsequently, a diethyl ether (10 ml) solution of compound (T-9) (2.68 g) was added dropwise in a temperature range of −70° C. to −65° C., and stirring was carried out for 4 hours while returning to room temperature. The resultant reaction mixture was poured into ice water (100 ml), and mixing was carried out. Toluene (100 ml) was added to separate layers into an organic layer and an aqueous layer, and an extraction operation was performed. The resultant organic layer was sequentially washed with a 1 N hydrochloric acid solution, a saturated aqueous solution of sodium hydrogencarbonate and water, and drying over anhydrous magnesium sulfate was carried out. The resultant solution was concentrated under reduced pressure, and a residue was purified by fractionation by means of column chromatography (silica gel; heptane), and further purified by recrystallization from a heptane/Solmix A-11 mixed solvent, and thus (E)-1-(1,2-difluoro-2-[3-fluoro-4-(trifluoromethyl)phenyl]vinyl)-2-fluoro-4-(4-propylcyclohexyl)benzene (1-1-25) (2.24 g) was obtained. The yield based on compound (T-9) was 57%.

Workup

  1. temperaturecooling
  2. customwas carried out to −70° C
  3. stirringstirring
  4. waitwas carried out for 4 hours
  5. customwhile returning to room temperature
  6. customThe resultant reaction mixture
  7. additionmixing
  8. customto separate layers into an organic layer
  9. washThe resultant organic layer was sequentially washed with a 1 N hydrochloric acid solution
  10. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and water, and drying over anhydrous magnesium sulfate
  11. concentrationThe resultant solution was concentrated under reduced pressure
  12. customa residue was purified by fractionation by means of column chromatography (silica gel; heptane)
  13. customfurther purified by recrystallization from a heptane/Solmix A-11
  14. additionmixed solvent

Sources & evidence

ORD record
ord-7a46b67f1c594af8ae3b3a561eca5abc
Source dataset
uspto-grants-2015_01
Patent number
US08940185B2

Reaction notes

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