p-Toluenesulfonic acid → 8-(4-Butoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decane

HRID 1886717Notes

Reaction equation

HRID 1886717 reaction equation
[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2(O)[CH2:21][CH2:20][C:15]3([O:19][CH2:18][CH2:17][O:16]3)[CH2:14][CH2:13]2)=[C:8]([F:23])[C:7]=1[F:24])[CH2:2][CH2:3][CH3:4].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]2[CH2:21][CH2:20][C:15]3([O:16][CH2:17][CH2:18][O:19]3)[CH2:14][CH2:13]2)=[C:8]([F:23])[C:7]=1[F:24])[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 666823378-(4-Butoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decan-8-ol

Product 1

HCID 666817408-(4-Butoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decaneYield 91.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
30 °C

Procedure

The compound (9) (55.0 g), p-toluenesulfonic acid (1.8 g) and toluene (300 ml) were mixed and the mixture was heated to reflux for 2 hours, while distilled water was removed. After the reaction mixture had been cooled to 30° C., water (500 ml) and toluene (900 ml) were added to the mixture and mixed with it. The mixture was then allowed to stand until it had separated into two phases of organic and aqueous phases, and the extraction into an organic phase was carried out. The resulting organic phase was separated, and washed successively with a saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate. The resulting solution was purified with a fractional operation by means of column chromatography using silica gel as a stationary phase powder and toluene as an eluent. The product was dissolved in a mixed solvent of toluene (150 ml) and Solmix A-11 (150 ml), and palladium on carbon (3.0 g) was added and then the mixture was stirred at room temperature under an atmosphere of hydrogen until hydrogen absorption had ceased. After the completion of the reaction, palladium on carbon was removed and the solvent was distilled off. The resulting residue was purified with a fractional operation by means of column chromatography using silica gel as a stationary phase powder and heptane as an eluent. The product was further purified by recrystallization from Solmix A-11 to give 8-(4-butoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decane (10) (47.8 g). The yield based on the compound (9) was 84.0%.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 2 hours
  3. distillationwhile distilled water
  4. customwas removed
  5. additionwater (500 ml) and toluene (900 ml) were added to the mixture
  6. additionmixed with it
  7. customhad separated into two phases of organic and aqueous phases
  8. extractionthe extraction into an organic phase
  9. customThe resulting organic phase was separated
  10. washwashed successively with a saturated aqueous solution of sodium hydrogencarbonate and water
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customThe resulting solution was purified with a fractional operation by means of column chromatography
  13. dissolutionThe product was dissolved in a mixed solvent of toluene (150 ml) and Solmix A-11 (150 ml), and palladium on carbon (3.0 g)
  14. additionwas added
  15. customAfter the completion of the reaction, palladium on carbon
  16. customwas removed
  17. distillationthe solvent was distilled off
  18. customThe resulting residue was purified with a fractional operation by means of column chromatography
  19. customThe product was further purified by recrystallization from Solmix A-11

Sources & evidence

ORD record
ord-069dc2adce2b4bfda84c2c49f59b3fcf
Source dataset
uspto-grants-2013_08
Patent number
US08501038B2

Reaction notes

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