Water → HCID 178447923, compound

HRID 1406825Notes

Reaction equation

HRID 1406825 reaction equation
O[C:2]1([C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([F:18])[CH:12]=2)[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][CH3:10])[CH2:4][CH2:3]1.O>C1(C)C=CC=CC=1>[CH2:8]([C@H:5]1[CH2:4][CH2:3][C@H:2]([C:11]2[CH:12]=[C:13]([F:18])[CH:14]=[C:15]([F:17])[CH:16]=2)[CH2:7][CH2:6]1)[CH2:9][CH3:10]

Participants

4

Reactant 2

HCID 962WaterHCID 55115836HCID 55115836, compound

Product 1

HCID 178447923HCID 178447923, compoundYield 46.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

In a nitrogen atmosphere, 132 g of crude 1-(1-hydroxy-4-propylcyclohexyl)-3,5-difluorobenzene and 2.99 g of p-toluenesulfonic monohydrate were dissolved in 250 mL of toluene, and the resultant solution was stirred for 2 hours under reflux while the produced water was removed. After the solution was allowed to cool to room temperature, an organic layer was washed with a saturated aqueous sodium bicarbonate solution and saturated brine, and dried by adding sodium sulfate, and then the solvent was distilled off under reduced pressure. Then, the whole amount of the resultant residue was dissolved in 280 mL of ethyl acetate, and 7.1 g of palladium 5%/carbon was added to the solution, followed by stirring in a hydrogen atmosphere at 5 Mpa for 6 hours. After the palladium catalyst was filtered off, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography. Then, the whole amount of the resultant product and 3.39 g of tertiary butoxypotassium were dissolved in 350 mL of DMF, followed by stirring at room temperature for 4 hours. Then, water and hexane were added to separate an organic layer. Further, an aqueous layer was subjected to extraction with hexane, and the hexane extract was combined with the organic layer and washed with saturated brine. The resultant mixture was dried by adding sodium sulfate, the solvent was distilled off, and distillation under reduced pressure (206 Pa, b. p.=110° C. to 112° C.) yielded 58.05 g of 1-(trans-4-propylcyclohexyl)-3,5-difluorobenzene.

Workup

  1. customwas removed
  2. washan organic layer was washed with a saturated aqueous sodium bicarbonate solution and saturated brine
  3. customdried
  4. additionby adding sodium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. dissolutionThen, the whole amount of the resultant residue was dissolved in 280 mL of ethyl acetate
  7. addition7.1 g of palladium 5%/carbon was added to the solution
  8. filtrationAfter the palladium catalyst was filtered off
  9. distillationthe solvent was distilled off under reduced pressure
  10. customthe residue was purified by silica gel column chromatography
  11. dissolutionThen, the whole amount of the resultant product and 3.39 g of tertiary butoxypotassium were dissolved in 350 mL of DMF
  12. stirringby stirring at room temperature for 4 hours
  13. additionThen, water and hexane were added
  14. customto separate an organic layer
  15. extractionFurther, an aqueous layer was subjected to extraction with hexane
  16. extractionthe hexane extract
  17. washwashed with saturated brine
  18. dry with materialThe resultant mixture was dried
  19. additionby adding sodium sulfate
  20. distillationthe solvent was distilled off
  21. distillationdistillation under reduced pressure (206 Pa, b. p.=110° C. to 112° C.)

Sources & evidence

ORD record
ord-034efcfe19954fb0b2ad303e0f13e3a1
Source dataset
uspto-grants-2014_12
Patent number
US08916718B2

Reaction notes

Loading…