Hydrochloric Acid → HCID 178466299, compound

Temperature

-10 °C

4-Ethoxy-2,3-difluorobenzyltriphenylphosphonium chloride (11) (dried; 24.9 g) and THF (100 ml) were mixed under a nitrogen atmosphere and cooled to −10° C. Then, potassium t-butoxide (t-BuOK) (5.4 g) was added thereto in twice in the temperature range of −10° C. to −5° C. The stirring was continued at −10° C. for 60 minutes, and then the compound (18) (10.0 g) dissolved in THF (30 ml) was added thereto dropwise in the temperature range of −10° C. to −5° C. The stirring was continued at 0° C. for 30 minutes, and then the reaction mixture was poured into a mixture of water (100 ml) and toluene (50 ml), and mixed. The mixture was then allowed to separate into organic and aqueous phases, and the extraction into an organic phase was carried out. The organic phase obtained was washed with water and dried over anhydrous magnesium sulfate. The solution obtained was concentrated under reduced pressure and the residue obtained was purified with a fractional operation by means of column chromatography (silica gel; toluene). The eluent obtained was concentrated under reduced pressure. Sodium benzenesulphinate dihydrate (2.6 g) was added, with stirring, to obtained light yellow crystals in Solmix A-11 (20 ml) and then 6N-hydrochloric acid (2.2 ml) was added, and the mixture was heated under reflux for 5 hours. The reaction mixture was cooled to 30° C., and water (100 ml) and toluene (100 ml) were added to the mixture obtained, and mixed. The mixture was then allowed to separate into organic and aqueous phases, and the extraction into an organic phase was carried out. The obtained organic phase were washed sequentially with water, aqueous 0.5 N-sodium hydroxide solution, a saturated aqueous solution of sodium hydrogencarbonate, and dried over anhydrous magnesium sulfate. The solution obtained was concentrated under reduced pressure and the residue obtained was purified by means of column chromatography (silica gel; heptane: toluene=2:3 by volume), and the eluent was concentrated under reduced pressure. The residue obtained was purified by means of recrystallization (heptane: Solmix=3:2 by volume), giving 10.6 g of 2,3-difluoro-4-ethoxy-[trans-4-(2,3-difluoro-4-ethoxyphenylethenyl)cyclohexyl]benzene (No. 228). The yield based on the compound (18) was 67.5%.

1. customtwice in the temperature range of −10° C. to −5° C
2. additionwas added
3. customdropwise in the temperature range of −10° C. to −5° C
4. waitThe stirring was continued at 0° C. for 30 minutes
5. additionmixed
6. customto separate into organic and aqueous phases
7. extractionthe extraction into an organic phase
8. customThe organic phase obtained
9. washwas washed with water
10. dry with materialdried over anhydrous magnesium sulfate
11. customThe solution obtained
12. concentrationwas concentrated under reduced pressure
13. customthe residue obtained
14. customwas purified with a fractional operation by means of column chromatography (silica gel; toluene)
15. customThe eluent obtained
16. concentrationwas concentrated under reduced pressure
17. additionSodium benzenesulphinate dihydrate (2.6 g) was added
18. customto obtained light yellow crystals in Solmix A-11 (20 ml)
19. temperaturethe mixture was heated
20. temperatureunder reflux for 5 hours
21. temperatureThe reaction mixture was cooled to 30° C.
22. customobtained
23. additionmixed
24. customto separate into organic and aqueous phases
25. extractionthe extraction into an organic phase
26. washThe obtained organic phase were washed sequentially with water, aqueous 0.5 N-sodium hydroxide solution
27. dry with materiala saturated aqueous solution of sodium hydrogencarbonate, and dried over anhydrous magnesium sulfate
28. customThe solution obtained
29. concentrationwas concentrated under reduced pressure
30. customthe residue obtained
31. customwas purified by means of column chromatography (silica gel; heptane: toluene=2:3 by volume)
32. concentrationthe eluent was concentrated under reduced pressure
33. customThe residue obtained
34. customwas purified by means of recrystallization (heptane: Solmix=3:2 by volume)

ORD record

ord-07b2727dd38b4d0f83d538fd5d9d6db9

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08216489B2