Water → 2-(2,3-Difluorophenethyl)-1,3-dioxolane

Temperature

-10 °C

Well-dried (1,3-dioxolan-2-yl)methyltriphenyl phosphonium bromide (s27) (108.8 g) was mixed with THF (500 ml) under an atmosphere of nitrogen, and cooled to −10° C. Potassium t-butoxide (t-BuOK; 28.4 g) was added in two portions in the temperature range of −10° C. to −5° C. After 60 minutes of stirring at −10° C., 2,3-difluorobenzaldehyde (s26) (30.0 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 treated with water, and the aqueous layer was extracted with toluene. The combined organic layers were washed with water, and then dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure, and the residue was purified by column chromatography with toluene as an eluent and silica gel as a stationary phase powder. The purified product was dissolved in a mixed solvent of toluene (250 ml) and Solmix A-11 (250 ml), to which Pd/C (1.5 g) was added. The mixture was stirred at room temperature under a hydrogen atmosphere until hydrogen absorption had ceased. After the reaction had been completed, Pd/C was removed, and then solvent was distilled off. The residue was purified by column chromatography with toluene as an eluent and silica gel as a stationary phase powder, and then by recrystallization from heptane to give 2-(2,3-difluorophenethyl)-1,3-dioxolane (s28) (37.9 g). The yield based on the compound (s26) was 83.8%.

1. additionwas added dropwise in the temperature range of −10 to −5° C
2. stirringAfter 30 minutes of stirring at 0° C.
3. extractionthe aqueous layer was extracted with toluene
4. washThe combined organic layers were washed with water
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationThe solution was concentrated under reduced pressure
7. customthe residue was purified by column chromatography with toluene as an eluent
8. dissolutionThe purified product was dissolved in a mixed solvent of toluene (250 ml) and Solmix A-11 (250 ml), to which Pd/C (1.5 g)
9. additionwas added
10. stirringThe mixture was stirred at room temperature under a hydrogen atmosphere until hydrogen absorption
11. customPd/C was removed
12. distillationsolvent was distilled off
13. customThe residue was purified by column chromatography with toluene as an eluent
14. customsilica gel as a stationary phase powder, and then by recrystallization from heptane

ORD record

ord-4088f24b085c4727917728a6aecf5e16

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580146B2