4-Ethoxy-2,3-difluorophenol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension prepared by suspending 1.52 g (38.0 mmol) of 60% sodium hydride in 15 ml of THF was added dropwise solution of 5.29 g (17.3 mmol) of the 4-(trans-4-n-pentylcyclohexyl)-phenyldithiocarboxylic acid obtained by the first step, in 20 ml of THF under a condition cooled with ice in 15 min, and stirred as it was for 30 min. To this reaction solution was added dropwise solution of 2.50 g (14.4 mmol) of 2,3-difluoro-4-ethoxyphenol in 20 ml of THF in 15 min and stirred as it was for 30 min. To this reaction solution was added dropwise solution of 9.64 g (38.0 mmol) of iodine in 20 ml of THF in 15 min, stirred as it was for 1 hour, warmed up to room temperature, and then stirred at the same temperature overnight. This reaction solution was poured into 10% aqueous sodium thiosulfate solution and extracted with 100 ml of diethyl ether. The organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under a reduced pressure, and the residue was purified by silica gel column chromatography (eluent: heptane) and further recrystallized from heptane to obtain 2.0 g of 2,3-difluoro-4-ethoxyphenyl 4-(trans-4-n-pentylcyclohexyl)thiobenzoate (yield 31.2%). To a suspension prepared cooled with ice in 15 min stirred as it was for 30 min stirred as it was for 1 hour stirred at the same temperature overnight extracted with 100 ml of diethyl ether The organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off under a reduced pressure the residue was purified by silica gel column chromatography (eluent: heptane) further recrystallized from heptane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The general procedure of Example 9 was repeated using 2,3-difluoro-4-ethoxyphenol and 4-bromomethyl-1-n-heptyl-1-phenyl-1-silacyclohexane, thereby obtaining the intended compound. obtaining the intended compound

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.02 mol of 2,3-difluoroethoxybenzene are metalated according to 1b. Subsequently, 0.02 mol of trimethyl borate are added dropwise at a temperature of about -55° to -60° C. during the course of 0.5 h. The resulting suspension is subsequently stirred for a further 0.5 h, the temperature climbing to about -20°. 1.5 ml of 98% acetic acid are added. After about 15 min, the mixture is cooled to about -35° and a solution of 30% H2O2 /H2O (5 ml/2 ml) is added dropwise. After stirring for 2 h while slowly warming to room temperature, the organic phase is separated and the aqueous phase is extracted with methyl tert.butyl ether. Finally, the mixture is washed with saturated NaCl solution, dried and evaporated. climbing to about -20° After about 15 min the mixture is cooled to about -35° After stirring for 2 h the organic phase is separated the aqueous phase is extracted with methyl tert.butyl ether Finally, the mixture is washed with saturated NaCl solution dried evaporated

反応条件: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Ethoxy-2,3-difluorophenol (6) (2.2 g) and tripotassium phosphate (K3PO4) (11.0 g) were added to DMF (100 ml) under a nitrogen atmosphere, and the stirring was continued at 70° C. The compound (20) (3.0 g) was added thereto, and the stirring was continued at 70° C. for 7 hours. After the reaction mixture obtained had been cooled to 30° C. and separated from the solid by filtration, toluene (100 ml) and water (100 ml) were added thereto and mixed. The mixture was then allowed to separate into organic and aqueous phases. The extraction into an organic phase was carried out. The organic phase obtained was washed with brine and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off, and the residue obtained was purified by means of column chromatography (silica gel/toluene=1/2 by volume). The product was further purified by means of recrystallization (Solmix A-11: heptane=1:2 by volume), giving 2.2 g of 1-(4-ethoxy-2,3-difluorophenyl)-4-(4-ethoxy-2,3-difluorophenoxymethyl)-cyclohexane (No. 828). The yield based on the compound (20) was 74.0%. was continued at 70° C After the reaction mixture obtained separated from the solid by filtration, toluene (100 ml) and water (100 ml) were added mixed to separate into organic and aqueous phases The extraction into an organic phase The organic phase obtained was washed with brine dried over anhydrous magnesium sulfate Then, the solvent was distilled off the residue obtained was purified by means of column chromatography (silica gel/toluene=1/2 by volume) The product was further purified by means of recrystallization (Solmix A-11: heptane=1:2 by volume)

反応条件: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Ethoxy-2,3-difluorophenol (6) (1.5 g) and tripotassium phosphate (K3PO4) (7.5 g) were added to DMF (100 ml) under a nitrogen atmosphere, and the stirring was continued at 70° C. The compound (5) (2.0 g) was added thereto and the stirring was continued at 70° C. for 7 hours. After the reaction mixture obtained had been cooled to 30° C. and then separated from the solid by filtration, toluene (100 ml) and water (100 ml) were added thereto and mixed. The mixture was then allowed to stand until it had separated into two phases of organic and aqueous phases. The extraction into an organic phase was carried out. The organic phase obtained was washed with brine and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off, and the residue obtained was purified by means of column chromatography (silica gel; heptane: toluene=1:2 by volume). The product was further purified by means of recrystallization from a mixed solvent of Solmix A-11 and heptane (Solmix A-11: heptane=1:2 by volume) and dried, giving 2.2 g of 4-ethoxy-2,3-difluoro-4′-(4-ethoxy-2,3-difluorophenoxymethyl)-1,1′-biphenyl (No. 678). The yield based on the compound (5) was 74.0%. was continued at 70° C After the reaction mixture obtained separated from the solid by filtration, toluene (100 ml) and water (100 ml) were added mixed had separated into two phases of organic and aqueous phases The extraction into an organic phase The organic phase obtained was washed with brine dried over anhydrous magnesium sulfate Then, the solvent was distilled off the residue obtained was purified by means of column chromatography (silica gel; heptane: toluene=1:2 by volume) The product was further purified by means of recrystallization from a mixed solvent of Solmix A-11 and heptane (Solmix A-11: heptane=1:2 by volume) dried

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9.8 g of trans-4-(trans-4-vinylcyclohexyl)cyclohexylmethyl methanesulfonate and 5.96 g of 2,3-difluoro-4-ethoxyphenol were dissolved in 90 mL of DMF. 10.4 g of tripotassium phosphate was added, followed by stirring at 90 to 100° C. for 3 hours. The reaction mixture was poured into water, extracted with toluene, washed in turn with water, 10% hydrochloric acid, water, and saturated saline and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified in turn by subjecting to column chromatography (silica gel/toluene), recrystallization (methanol/acetone), column chromatography (alumina/acetone), washing with ion-exchange water, silica treatment, and recrystallization (methanol/acetone) to obtain 8.5 g of 4-ethoxy-2,3-difluoro-1-(trans-4-(trans-4-vinylcyclohexyl)cyclohexyl)methoxybenzene (IIIa) as a colorless crystal. extracted with toluene washed in turn with water, 10% hydrochloric acid, water, and saturated saline dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure the residue was purified in turn by subjecting to column chromatography (silica gel/toluene), recrystallization (methanol/acetone), column chromatography (alumina/acetone) washing with ion-exchange water, silica treatment, and recrystallization (methanol/acetone)

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9.8 g of trans-4-(trans-4-vinylcyclohexyl)cyclohexylmethyl methanesulfonate and 5.96 g of 2,3-difluoro-4-ethoxyphenol were dissolved in 90 mL of DMF. 10.4 g of tripotassium phosphate was added, followed by stirring at 90 to 100° C. for 3 hours. The reaction mixture was poured into water, extracted with toluene, washed in turn with water, 10% hydrochloric acid, water, and saturated saline and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified in turn by subjecting to column chromatography (silica gel/toluene), recrystallization (methanol/acetone), column chromatography (alumina/acetone), washing with ion-exchange water, silica treatment, and recrystallization (methanol/acetone) to obtain 8.5 g of 4-ethoxy-2,3-difluoro-1-(trans-4-(trans-4-vinylcyclohexyl)cyclohexyl)methoxybenzene (IIIa) as a colorless crystal. extracted with toluene washed in turn with water, 10% hydrochloric acid, water, and saturated saline dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure the residue was purified in turn by subjecting to column chromatography (silica gel/toluene), recrystallization (methanol/acetone), column chromatography (alumina/acetone) washing with ion-exchange water, silica treatment, and recrystallization (methanol/acetone)