Water → HCID 68008782, compound

Temperature

-10 °C

Well-dried (2,3-difluoro-4-hexyloxybenzyl)triphenylphosphonium chloride (s-16) (7.5 g) and THF (100 ml) were mixed under an atmosphere of nitrogen, which was cooled to −10° C. Potassium t-butoxide (t-BuOK; 1.6 g) was added in the temperature range of −10° C. to −5° C. After 60 minutes of stirring at −10° C., 2,3-difluorobenzaldehyde (s-23) (1.9 g) dissolved in THF (30 ml) was added dropwise in the temperature range of −10 to −5° C. After 30 minutes of stirring at 0° C., the reaction mixture was poured into a mixture of water (100 ml) and toluene (100 ml) and mixed with them. 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 water, and then dried over anhydrous magnesium sulfate. The resulting solution was concentrated under reduced pressure. The resulting residue was purified by column chromatography using silica gel as a stationary phase powder and toluene as an eluent, and the eluent was concentrated under reduced pressure. The residue was dissolved in a mixed solvent of toluene (100 ml) and Solmix A-11 (100 ml), and Pd/C (0.1 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 recrystallization from a mixed solvent of ethyl acetate and Solmix A-11 (ethyl acetate:Solmix=1:4 by volume) to give 1-(2,3-difluorophenethyl)-2,3-difluoro-4-(hexyloxy)benzene (s-24) (3.6 g). The yield based on the compound (s-23) was 76.0%.

1. additionwas added dropwise in the temperature range of −10 to −5° C
2. stirringAfter 30 minutes of stirring at 0° C.
3. additionmixed with them
4. customhad separated into two layers of organic and aqueous layers
5. extractionthe extraction into an organic layer
6. customThe resulting organic layers were separated
7. washwashed with water
8. dry with materialdried over anhydrous magnesium sulfate
9. concentrationThe resulting solution was concentrated under reduced pressure
10. customThe resulting residue was purified by column chromatography
11. concentrationthe eluent was concentrated under reduced pressure
12. dissolutionThe residue was dissolved in a mixed solvent of toluene (100 ml) and Solmix A-11 (100 ml), and Pd/C (0.1 g)
13. additionwas added
14. stirringThe mixture was stirred at room temperature under a hydrogen atmosphere until hydrogen absorption
15. customAfter the completion of the reaction, Pd/C
16. customwas removed
17. distillationthe solvent was distilled off
18. customThe resulting residue was purified by recrystallization from a mixed solvent of ethyl acetate and Solmix A-11 (ethyl acetate:Solmix=1:4 by volume)

ORD record

ord-fb1bb210e1214844a7a303a7bb342c7b

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580147B2