Toluene → 8-{4-[2-Fluoro-4-(4-pentyl-cyclohexyl)-phenyl]-cyclohex-3-enyl}-1,4-dioxa-spiro[4,5] decane

HRID 1095236Notes

Reaction equation

HRID 1095236 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([CH:11]3[CH2:16][CH2:15][C:14]([C:18]4[CH:23]=[CH:22][C:21]([C:24]5(CCCCC)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]5)=[CH:20][C:19]=4[F:35])(O)[CH2:13][CH2:12]3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[C:36]1(C)[CH:41]=[CH:40]C(S(O)(=O)=O)=[CH:38][CH:37]=1.C1(C)C=CC=CC=1>O>[F:35][C:19]1[CH:20]=[C:21]([CH:24]2[CH2:25][CH2:26][CH:27]([CH2:38][CH2:37][CH2:36][CH2:41][CH3:40])[CH2:28][CH2:29]2)[CH:22]=[CH:23][C:18]=1[C:14]1[CH2:13][CH2:12][CH:11]([CH:8]2[CH2:9][CH2:10][C:5]3([O:4][CH2:3][CH2:2][O:1]3)[CH2:6][CH2:7]2)[CH2:16][CH:15]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 6101p-Toluenesulfonic acidHCID 667819884-(1,4-Dioxa-spiro[4,5] dec-8-yl)-1-[2-fluoro-4-(pentyl-cyclohexyl)-phenyl]-cyclohexanol

Product 1

HCID 582122828-{4-[2-Fluoro-4-(4-pentyl-cyclohexyl)-phenyl]-cyclohex-3-enyl}-1,4-dioxa-spiro[4,5] decaneYield 537.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
30 °C

Procedure

The compound (3) (108.6 g), p-toluenesulfonic acid (4.02 g) and toluene (500 ml) were mixed, and the mixture was heated under reflux for 1.5 hours while the water being distilled was removed. The reaction mixture was cooled to 30° C., and then water (1,000 ml) and toluene (1,800 ml) were added and mixed with it. The mixture was then allowed to stand until it had separated into two phases, the organic and aqueous phases, and an extractive operation to an organic phase was carried out. The organic phase was fractionated, and washed sequentially with a saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate. The solvent of the solution was distilled off under reduced pressure, and the residue was purified with a fractional operation by means of column chromatography using a mixed solvent of toluene and ethyl acetate (toluene:ethyl acetate=7:3 by volume) as an eluent and silica gel as a stationary phase powder, and further purified by means of recrystallization from heptane and dried, giving 58.8 g of 8-{4-[2-fluoro-4-(4-pentyl-cyclohexyl)-phenyl]-cyclohex-3-enyl}-1,4-dioxa-spiro[4,5] decane (4). The yield based on the compound (1) was 53.4%.

Workup

  1. temperaturethe mixture was heated
  2. distillationdistilled
  3. customwas removed
  4. additionwater (1,000 ml) and toluene (1,800 ml) were added
  5. additionmixed with it
  6. customhad separated into two phases
  7. washwashed sequentially with a saturated aqueous solution of sodium hydrogencarbonate and water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. distillationThe solvent of the solution was distilled off under reduced pressure
  10. customthe residue was purified with a fractional operation by means of column chromatography
  11. customsilica gel as a stationary phase powder, and further purified by means of recrystallization from heptane
  12. customdried

Sources & evidence

ORD record
ord-976620f664f54b5796d100802653f6ad
Source dataset
uspto-grants-2012_03
Patent number
US08137583B2

Reaction notes

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