Toluene → 1-(4-(2,3-Difluoro-4-(4-pentylcyclohexyl)phenyl)cyclohex-3-enyl)-4-ethoxy-2,3-difluorobenzene

HRID 1943560Notes

Reaction equation

HRID 1943560 reaction equation
[F:1][C:2]1[C:7]([F:8])=[C:6]([CH:9]2[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH2:11][CH2:10]2)[CH:5]=[CH:4][C:3]=1[C:20]1(O)[CH2:25][CH2:24][CH:23]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH3:34])=[C:28]([F:35])[C:27]=2[F:36])[CH2:22][CH2:21]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>O>[F:1][C:2]1[C:7]([F:8])=[C:6]([CH:9]2[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH2:11][CH2:10]2)[CH:5]=[CH:4][C:3]=1[C:20]1[CH2:25][CH2:24][CH:23]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH3:34])=[C:28]([F:35])[C:27]=2[F:36])[CH2:22][CH:21]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 6101p-Toluenesulfonic acidHCID 670824391-(2,3-Difluoro-4-(4-pentylcyclohexyl)phenyl)-4-(4-ethoxy-2,3-difluorophenyl)cyclohexanol

Product 1

HCID 670825171-(4-(2,3-Difluoro-4-(4-pentylcyclohexyl)phenyl)cyclohex-3-enyl)-4-ethoxy-2,3-difluorobenzeneYield 50.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
30 °C

Procedure

The compound (51) (9.7 g), p-toluenesulfonic acid (0.15 g) and toluene (200 ml) were mixed, and the mixture was heated under reflux for 2 hours while water being distilled was removed. The reaction mixture was cooled to 30° C., and then water (200 ml) and toluene (300 ml) were added thereto and mixed. The mixture was then allowed to stand until it had separated into two phases of organic and aqueous phases, and extraction into an organic phase was carried out. The organic phase obtained was fractionated, washed sequentially with a saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate. The solution obtained was purified with a fractional operation by means of column chromatography using a mixed solvent of heptane and toluene (heptane:toluene=2:3 by volume) as the eluent and silica gel as the stationary phase powder. The solvent was distilled off, and the residue obtained was purified with a fractional operation by means of column chromatography using toluene as the eluent and silica gel as the stationary phase powder. The product was further purified by means of recrystallization from a mixed solvent of Solmix A-11 and ethyl acetate (Solmix A-11:ethyl acetate=2:1 by volume) and dried, giving 4.7 g of 1-(4-(2,3-difluoro-4-(4-pentylcyclohexyl)phenyl)cyclohex-3-enyl)-4-ethoxy-2,3-difluorobenzene (No. 12). The yield based on the compound (10) was 49.8%.

Workup

  1. temperaturethe mixture was heated
  2. distillationdistilled
  3. customwas removed
  4. additionwater (200 ml) and toluene (300 ml) were added
  5. additionmixed
  6. customhad separated into two phases of organic and
  7. extractionaqueous phases, and extraction into an organic phase
  8. customThe organic phase obtained
  9. washwashed sequentially with a saturated aqueous solution of sodium hydrogencarbonate and water
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solution obtained
  12. customwas purified with a fractional operation by means of column chromatography
  13. distillationThe solvent was distilled off
  14. customthe residue obtained
  15. customwas purified with a fractional operation by means of column chromatography
  16. customThe product was further purified by means of recrystallization from a mixed solvent of Solmix A-11 and ethyl acetate (Solmix A-11:ethyl acetate=2:1 by volume)
  17. customdried

Sources & evidence

ORD record
ord-b2619aeb3df84aa9876b6f8dcf0282fb
Source dataset
uspto-grants-2013_03
Patent number
US08394294B2

Reaction notes

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