Reaktion #2126582

Reaktionsgleichung

sec-Butyllithium

1,4-Dioxaspiro[4.5]decan-8-one

ammonium chloride

1,2-Difluoro-3-hexyloxybenzene

→

8-(2,3-difluoro-4-hexyloxyphenyl)-1,4-dioxaspiro[4.5]decane

Ausbeute 87.3%

Lösungsmittel

THF

ethyl acetate

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added dropwise in the temperature range of −74° C. to −70° C.
2. 2
   workup.WAITthe stirring was continued for 8 hours while the mixture
3. 3
   Sonstigeto return to 25° C
4. 4
   SonstigeThe resulting reaction mixture
5. 5
   workup.ADDITIONwas poured into a vessel
6. 6
   workup.ADDITIONmixed with them
7. 7
   Sonstigehad separated into organic and aqueous layers
8. 8
   Extraktionthe extraction
9. 9
   SonstigeThe resulting organic layers were separated
10. 10
    Waschenwashed with water
11. 11
    Trocknena saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate
12. 12
    workup.DISTILLATIONThe solvent was distilled off under reduced pressure
13. 13
    workup.ADDITIONp-Toluenesulfonic acid (4.5 g) and toluene (300 ml) were mixed with the residue
14. 14
    Temperaturthe mixture was heated
15. 15
    Temperaturto reflux for 2 hours
16. 16
    workup.DISTILLATIONwhile distilled water
17. 17
    Sonstigewas removed
18. 18
    workup.ADDITIONwater (500 ml) and toluene (900 ml) were added
19. 19
    workup.ADDITIONmixed with it
20. 20
    Sonstigehad separated into two layers of organic and aqueous layers
21. 21
    Extraktionthe extraction into an organic layer
22. 22
    SonstigeThe resulting organic layers were separated
23. 23
    Waschenwashed with a saturated aqueous solution of sodium hydrogencarbonate and water
24. 24
    Trocknendried over anhydrous magnesium sulfate
25. 25
    SonstigeThe resulting solution was purified by column chromatography
26. 26
    workup.DISSOLUTIONThe product was dissolved in a mixed solvent of toluene (250 ml) and Solmix A-11 (250 ml), and Pd/C (0.5 g)
27. 27
    workup.ADDITIONwas added
28. 28
    SonstigeAfter the completion of the reaction, Pd/C
29. 29
    Sonstigewas removed
30. 30
    workup.DISTILLATIONthe solvent was distilled off
31. 31
    SonstigeThe resulting residue was purified by column chromatography
32. 32
    Sonstigefurther purified by recrystallization from heptane
33. 33
    Sonstigedried

Vorschrift

1,2-Difluoro-3-hexyloxybenzene (s-1) (100.0 g) and THF (1,000 ml) were placed in a reaction vessel under an atmosphere of nitrogen, and cooled to −74° C. sec-Butyllithium (1.00M; n-hexane and cyclohexane solution; 357 ml) was added dropwise in the temperature range of −74° C. to −70° C., and the stirring was continued for another 2 hours. 1,4-Dioxaspiro[4.5]decan-8-one (s-2) (72.9 g) in a THF (500 ml) solution was added dropwise in the temperature range of −75° C. to −70° C., and the stirring was continued for 8 hours while the mixture was allowed to return to 25° C. The resulting reaction mixture was poured into a vessel containing an aqueous solution of ammonium chloride (1,000 ml) and ethyl acetate (1,000 ml) and mixed with them. The mixture was then allowed to stand until it had separated into organic and aqueous layers, and the extraction was carried out. The resulting organic layers were separated, and washed with water, a saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. p-Toluenesulfonic acid (4.5 g) and toluene (300 ml) were mixed with the residue, and the mixture was heated to reflux for 2 hours, while distilled water was removed. After the reaction solution had been cooled to 30° C., water (500 ml) and toluene (900 ml) were added and mixed with it. The mixture was then allowed to stand until it had separated into two layers of organic and aqueous layers, and the extraction into an organic layer was carried out. The resulting organic layers were separated, and washed with a saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate. The resulting solution was purified by 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 (250 ml) and Solmix A-11 (250 ml), and Pd/C (0.5 g) was added. The mixture was stirred at room temperature under a hydrogen atmosphere until hydrogen absorption had ceased. After the completion of the reaction, Pd/C was removed, and the solvent was distilled off. The resulting residue was purified by column chromatography using silica gel as a stationary phase powder and toluene as an eluent, and further purified by recrystallization from heptane and dried to give 8-(2,3-difluoro-4-hexyloxyphenyl)-1,4-dioxaspiro[4.5]decane (s-3) (144.5 g). The yield based on the compound (s-1) was 87.3%.

Quelle