Potassium Carbonate → HCID 86682757, compound

HRID 1912240Notes

Reaction equation

HRID 1912240 reaction equation
Br[C:2]([F:23])([F:22])[C:3]1[C:8]([F:9])=[CH:7][C:6]([C:10]23[O:17][CH2:16][C:13]([CH2:18][CH2:19][CH3:20])([CH2:14][O:15]2)[CH2:12][O:11]3)=[CH:5][C:4]=1[F:21].[F:24][C:25]1[CH:26]=[C:27]([OH:33])[CH:28]=[C:29]([F:32])[C:30]=1[F:31].C(=O)([O-])[O-].[K+].[K+]>[Br-].C([P+](CCCC)(CCCC)CCCC)CCC.O.C1(C)C=CC=CC=1.CCCCCCC>[F:22][C:2]([F:23])([O:33][C:27]1[CH:26]=[C:25]([F:24])[C:30]([F:31])=[C:29]([F:32])[CH:28]=1)[C:3]1[C:8]([F:9])=[CH:7][C:6]([C:10]23[O:17][CH2:16][C:13]([CH2:18][CH2:19][CH3:20])([CH2:14][O:15]2)[CH2:12][O:11]3)=[CH:5][C:4]=1[F:21]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 27779433,4,5-TrifluorophenolHCID 86682758HCID 86682758, compound

Product 1

HCID 86682757HCID 86682757, compoundYield 50.4%

Reagents, catalysts & solvents 4

HCID 76564Tetrabutylphosphonium bromideCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8900HeptaneSolvent

Conditions

Temperature
83.5 °C

Procedure

In a reactor under an N2-atmosphere, 10.0 g (25.1 mmol) 1-(4-(bromodifluoro-methyl)-3,5-difluorophenyl)-4-propyl-2,6,7-trioxabicyclo[2.2.2]octane, 4.5 g (30 mmol) of 3,4,5-trifluorophenol, 3.5 g (25 mmol) of potassium carbonate, 2.6 g (7.5 mmol) of tetrabutylphosphonium bromide, 50 ml of H2O and 5 ml of n-heptane were added, and the mixture was refluxed at 82-85° C. for 10 hours. After being cooled to room temperature, the mixture was added with 100 ml of toluene and 100 ml of water, the organic layer was separated, and then the water layer was subjected to extraction with toluene. The organic layer was collected, washed by an aqueous solution of sodium hydrogen carbonate and water in sequence, dried over anhydrous magnesium sulfate, filtered to remove insoluble substance, and concentrated at a reduced pressure. The residue was purified by a fractionation operation utilizing column chromatography, with a mixed solvent of heptane and ethyl acetate in a volume ratio of 1:4 (ethyl acetate:heptane) as an eluent solvent and silica gel as a filler. The product was further purified by recrystallization using isopropanol/ethyl acetate in a volume ratio of 80/20, so that 5.9 g of 1-(4-(difluoro(3,4,5-trifluorophenoxy)methyl)-3,5-difluorophenyl)-4-propyl-2,6,7-trioxabicyclo[2.2.2]octane was obtained as a white solid.

Workup

  1. temperatureAfter being cooled to room temperature
  2. customthe organic layer was separated
  3. extractionthe water layer was subjected to extraction with toluene
  4. customThe organic layer was collected
  5. washwashed by an aqueous solution of sodium hydrogen carbonate and water in sequence
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customto remove insoluble substance
  9. concentrationconcentrated at a reduced pressure
  10. customThe residue was purified by a fractionation operation utilizing column chromatography, with a mixed solvent of heptane and ethyl acetate in a volume ratio of 1:4 (ethyl acetate:heptane) as an eluent solvent and silica gel as a filler
  11. customThe product was further purified by recrystallization

Sources & evidence

ORD record
ord-f506e262bf304cad9cf1a77ad3c13dbd
Source dataset
uspto-grants-2013_12
Patent number
US08609208B2

Reaction notes

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