Water → HCID 178466279, compound

Participants

Reaction Conditions

Reaction Steps

Well-dried 3-(4-ethoxy-2,3-difluorophenyl)propyl triphenylphosphonium bromide (s23) (6.6 g) was mixed with THF (100 ml) under an atmosphere of nitrogen, and the solution was cooled to −10° C. Potassium t-butoxide (t-BuOK; 1.4 g) was added in two portions in the temperature range of −10° C. to −5° C. After 60 minutes of stirring at −10° C., the compound (s25) (3.0 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 mixed with sodium benzenesulfonate dihydrate (6.1 g) and Solmix A-11 (100 ml). Then, 6N-hydrochloric acid (20 ml) was added, and the mixture was heated to reflux for 2 hours. The reaction mixture was treated with water, and the aqueous layer was extracted with toluene (100 ml). The combined organic layers were 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, and 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 a mixed solvent of ethyl acetate and Solmix A-11 (ethyl acetate:Solmix=1:4 by volume) to give (E)-1-ethoxy-2,3-difluoro-4-(4-(trans-4-(4-ethoxy-2,3-difluorophenyl)cyclohexyl)but-3-en-1-yl)benzene (No. 82) (4.6 g). The yield based on the compound (s13) was 41.9%.

Provenance & Evidence