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With tetrabutylammomium bromide; sodium hydroxide In water at 80℃; for 6 h; Inert atmosphere
To an aqueous (400 ml) solution of 4-bromo-2,3-difluorophenol (T-1) (195.0 g), bromoethane (196.2 g) and tetrabutylammonium bromide (hereinafter, abbreviated as TBAB) (24.2 g), sodium hydroxide (75.9 g) was added, and heating agitation was carried out at 80° C for 6 hours in a nitrogen atmosphere. After completion of the reaction, extraction was carried out with heptane, an organic layer was washed with water and a saturated aqueous solution of sodium chloride, and then the resultant solution was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and thus a black oily matter was obtained. The resultant material was purified by distillation, and thus 1-ethoxy-2,3-difluorobromobenzene (T-2) was obtained as a colorless oily matter (230.0 g, yield: 97percent).
97%
With tetrabutylammomium bromide; sodium hydroxide In water at 80℃; for 6 h; Inert atmosphere
To a water (400 ml) solution of 4-bromo-2,3-difluorophenol (T-1) (195.0 g), bromoethane (196.2 g) and tetrabutylammonium bromide (hereinafter referred to as TBAB) , Sodium hydroxide (75.9 g) were added, and the mixture was heated and stirred at 80 ° C. for 6 hours under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was extracted with heptane. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a black oil. This product was purified by distillation to give 1-ethoxy-2,3-difluorobromobenzene (T-2) as a colorless oil (230.0 g, yield 97percent).
Stage #1: With n-butyllithium In tetrahydrofuran at -70℃; for 2 h; Inert atmosphere Stage #2: at -70 - 20℃; for 16 h; Stage #3: With hydrogenchloride In tetrahydrofuran; water
According to the synthetic scheme shown above, compound (T-2) (129.5 g) obtained as an intermediate of Example 1 was dissolved in DryTHF (500 ml), and the resultant solution was cooled to -70°C. In a nitrogen atmosphere, n-BuLi (500 ml) was added dropwise, and agitation was carried out at -70°C for 2 hours. Then, a DryTHF solution of trimethyl borate (129.5 g) was slowly added dropwise at -70°C, and the resultant solution was heated to room temperature and agitated for 16 hours. After completion of the reaction, 2N-HCl (200 ml) was added, and then extraction was carried out with toluene, an organic layer was washed with water and a saturated aqueous solution of sodium chloride, and then the resultant solution was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and thus a light brown solid was obtained. The resultant material was subjected to recrystallization (heptane: toluene = 4 : 1 in a volume ratio), and thus (T-20) was obtained as a colorless crystal (117.2 g, yield: 71percent).
71%
Stage #1: With n-butyllithium In tetrahydrofuran at -70℃; for 2 h; Inert atmosphere Stage #2: at -70 - 20℃; for 16 h; Inert atmosphere
The compound (T-2) obtained in the above step(129.5 g) was dissolved in Dry THF (500 ml)It was cooled to -70 ° C.N-BuLi (500 ml) was added dropwise under a nitrogen atmosphere, and the mixture was stirred at -70 ° C. for 2 hours. Thereafter, a Dry THF solution of trimethyl borate (129.5 g) was slowly added dropwise at -70 ° C., the temperature was raised to room temperature, and the mixture was stirred for 16 hours.After completion of the reaction, 2N HCl (200 ml) was added and the mixture was extracted with toluene, washed with water and saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a light brown solid.This product was recrystallized (heptane: toluene = 4: 1 by volume ratio) to obtain (T-20) as colorless crystals (117.2 g, yield 71percent).
With ammonium chloride; magnesium; In tetrahydrofuran;
First Step: 6.1 g of well dried magnesium and 20 mL of THF were placed in a reactor under nitrogen atmosphere, and heated to 40° C. 59.7 g of <strong>[156573-09-0]1-bromo-4-ethoxy-2,3-difluorobenzene</strong> (1) dissolved in 300 mL of THF was slowly added dropwise thereto at a temperature range of from 40 to 60° C., followed by stirring for 60 minutes. Thereafter, 50.0 g of 4-(1,4-dioxaspiro[4,5]dec-8-yl)cyclohexanone (2) dissolved in 150 mL of THF was slowly added dropwise thereto at a temperature range of from 50 to 60° C., followed by stirring for 60 minutes. After cooling the resulting reaction mixture to 30° C., the reaction mixture was mixed with 900 mL of a 3percent ammonium chloride aqueous solution and 500 mL of toluene cooled to 0° C. in a vessel and separated into an organic layer and an aqueous layer by standing still, so as to attain extraction. The resulting organic layer was fractionated and washed with water, a saturated sodium bicarbonate aqueous solution, and water, followed by drying over anhydrous magnesium sulfate. Thereafter, the solvent was distilled off under reduced pressure to obtain 100.1 g of 4-(1,4-dioxaspiro[4,5]dec-8-yl)-1-(4-ethoxy-2,3-difluorophenyl)cyclohexanol (3). The resulting compound (3) was a yellow solid.
With hydrogenchloride; magnesium; In tetrahydrofuran; water; toluene;
Seventh Step: 1.76 g of well dried magnesium and 10 mL of THF were placed in a reactor under nitrogen atmosphere, and heated to 53 C. 17.2 g of the compound (1) dissolved in 30 mL of THF was slowly added dropwise thereto at a temperature range of from 50 to 56 C., followed by stirring for 30 minutes. Thereafter, 6.0 g of the compound (16) dissolved in 10 mL of THF was slowly added dropwise thereto at a temperature range of from 50 to 55 C., followed by stirring for 30 minutes. After cooling the resulting reaction mixture to 25 C., the reaction mixture was poured into and mixed with a mixture of 100 mL of 1N hydrochloric acid and 100 mL of toluene. The mixture was then separated into an organic layer and an aqueous layer by standing still, so as to attain extraction to the organic layer. The resulting organic layer was fractionated and washed with water, a 2N sodium hydroxide aqueous solution, a saturated sodium bicarbonate aqueous solution, and water, followed by drying over anhydrous magnesium sulfate. Thereafter, the solvent was removed by distillation under reduced pressure to obtain 18.5 g of 1-(4-ethoxy-2,3-difluorophenyl)-4-vinylcyclohexanol (17) as a yellow liquid.
Example 7 Properties of Liquid Crystal Compound (No. 132) A liquid crystal composition (v) including 85% by weight of the base mixtures (i) and 15% by weight of 4-(4-ethoxy-2,3-difluorophenyl)-trans-4'-vinylbicyclohexyl-3-ene (No. 132) obtained in Example 1 was prepared.
4
[ 156573-09-0 ]
[ 121-43-7 ]
[ 212386-71-5 ]
Yield
Reaction Conditions
Operation in experiment
71%
According to the synthetic scheme shown above, compound (T-2) (129.5 g) obtained as an intermediate of Example 1 was dissolved in DryTHF (500 ml), and the resultant solution was cooled to -70C. In a nitrogen atmosphere, n-BuLi (500 ml) was added dropwise, and agitation was carried out at -70C for 2 hours. Then, a DryTHF solution of trimethyl borate (129.5 g) was slowly added dropwise at -70C, and the resultant solution was heated to room temperature and agitated for 16 hours. After completion of the reaction, 2N-HCl (200 ml) was added, and then extraction was carried out with toluene, an organic layer was washed with water and a saturated aqueous solution of sodium chloride, and then the resultant solution was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and thus a light brown solid was obtained. The resultant material was subjected to recrystallization (heptane: toluene = 4 : 1 in a volume ratio), and thus (T-20) was obtained as a colorless crystal (117.2 g, yield: 71%).
71%
The compound (T-2) obtained in the above step(129.5 g) was dissolved in Dry THF (500 ml)It was cooled to -70 C.N-BuLi (500 ml) was added dropwise under a nitrogen atmosphere, and the mixture was stirred at -70 C. for 2 hours. Thereafter, a Dry THF solution of trimethyl borate (129.5 g) was slowly added dropwise at -70 C., the temperature was raised to room temperature, and the mixture was stirred for 16 hours.After completion of the reaction, 2N HCl (200 ml) was added and the mixture was extracted with toluene, washed with water and saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a light brown solid.This product was recrystallized (heptane: toluene = 4: 1 by volume ratio) to obtain (T-20) as colorless crystals (117.2 g, yield 71%).
In a reactor under nitrogen atmosphere, 50 ml of tetrahydrofuran (THF) was added to 6.15g of magnesium (Mg), followed by stirring at 44 C. 60.0 g of 1-bromo-4-etoxy-2,3-difluorobenzene (a1) dissolved in 130 ml of THF was added dropwise thereto in the temperature range of 38 C. to 49 C. for 1 hour. The resulting solution was added dropwise to a solution of 200 ml of THF and 39.5 g of trimethyl boratein the temperature range of -50 C. to -30 C. The reaction solution was injected into a mixture of 500 ml of 1N hydrochloric acid and 600 ml of ethyl acetate. The mixture was separated into organic layer and aqueous layer, and the organic layer was extracted. The resulting organic layer was washed with saturated chloride aqueous solution and dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to provide the residue. The resulting residue was purified by re-crystallization from a heptane, dried to provide 41.6 g of 4-ethoxy-2,3-difluorophenylboronic acid (a2) as a yellew solid.
First Step Magnesium (dried; 6.1 g) and THF (20 ml) were put in a reaction vessel under a nitrogen atmosphere, and heated to 40 C. 1-Bromo-4-ethoxy-2,3-difluorobenzene (12) (59.2 g) dissolved in THF (300 ml) was slowly added dropwise thereto in the temperature range of 40 C to 60 C, and the stirring was continued for another 60 minutes. Then, 1,4-dioxaspyro[4.5]decane-8-one (13) (30.0 g) dissolved in THF (150 ml) was slowly added dropwise in the temperature range of 50 C to 60 C, and the stirring was continued for another 60 minutes. The obtained reaction mixture was cooled to 30 C, poured into to a vessel containing an aqueous solution of ammonium chloride (3%; 900 ml) and toluene (500 ml) which were cooled to 0 C, and mixed. The mixture obtained was allowed to stand until it had separated into organic and aqueous phases, and the extraction into an organic phase was carried out. The organic phase obtained was washed sequentially with water, a saturated aqueous solution of sodium hydrogencarbonate and water, and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, giving 86.2 g of 8-(4-ethoxy-2,3-difluorophenyl)-1,4-dioxaspyro[4.5]decan-8-ol (14).
Compound (T-2) (142.2 g) obtained in the above step was dissolved in dry tetrahydrofuran (hereinafter, abbreviated as DryTHF) (500 ml), and the resultant solution was cooled to -70C, n-BuLi (364 ml) was added dropwise in a nitrogen atmosphere, and agitation was carried out at -70C for 2 hours. Then, a DryTHF solution of cyclohexanedione monoethylene ketal (T-3) (93.6 g) was slowly added dropwise, the resultant solution was heated to room temperature and agitated for 16 hours. After completion of the reaction, 2N-HCl (200 ml) was added, extraction was carried out with toluene, an organic layer was washed with water and a saturated aqueous solution of sodium chloride, and then the resultant solution was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and thus a light brown solid was obtained. The resultant material was dissolved in toluene (400 ml), p-TsOH (4.74 g) was added, and heating reflux was carried out for 4 hours while performing dehydration. After completion of the reaction, extraction was carried out with toluene, an organic layer was washed with water and a saturated aqueous solution of sodium chloride, and then the resultant solution was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and thus a light brown solid was obtained. The resultant material was subjected to silica gel column chromatography (heptane:ethyl acetate = 20:1 in a volume ratio) and recrystallization (Solmix), and thus (T-4) was obtained as a colorless crystal (126.1 g, yield: 71%).
With sodium hydroxide; tetrabutylammomium bromide; In water;
Preparation of 1-ethoxy-2,3-difluorobromobenzene (T-2) Sodium hydroxide (75.9 g) was added to a water (400 ml) solution of 4-bromo-2,3-difluorophenol (T-1) (195.0 g), bromoethane (196.2 g) and tetrabutylammonium bromide (hereinafter abbreviated as TBAB) (24.2 g), and the mixture was heated at 80 C. for 6 hours with stirring under an atmosphere of nitrogen. After the reaction had been completed, the reaction mixture was extracted with heptane and the organic layer was washed successively with water and brine, and dried over anhydrous magnesium sulfate. The extract was concentrated under reduced pressure to give a black oil. The oil was purified by distillation to give 1-ethoxy-2,3-difluorobromobenzene (T-2) (230.0 g, 97% yield) as a colorless oil.
3-butyl-1-(4-ethoxy-2,3-difluorophenyl)cyclopentanol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With ammonium chloride; In tetrahydrofuran; hexane;
Second Step THF (40 ml) was added to <strong>[156573-09-0]1-bromo-4-ethoxy-2,3-difluorobenzene</strong> (3.56 g) in a reaction vessel under an atmosphere of nitrogen, and the mixture was cooled to -78 C. n-Butyllithium (1.65 M, in a hexane solution) (9.1 ml) was added dropwise at a temperature of -70 C. or lower. The stirring was continued at -78 C. for another 1.5 hour and 3-butyl-cyclopentanone (2.1 g) obtained in the first step, in a THF (20 ml) solution was added dropwise at a temperature of -70 C. or lower. After the mixture had been stirred at -78 C. for another 1 hour, it was warmed to room temperature, and a saturated aqueous solution of ammonium chloride (50 ml) was added. The mixture was separated, and the water layer was extracted with diethyl ether three times, and then the combined organic layer was washed with brine. The solution was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (eluent: ethyl acetate/n-heptane= 1/9 by volume) to give 3-butyl-1-(4-ethoxy-2,3-difluorophenyl)cyclopentanol (2.8 g).
With ammonium chloride; In tetrahydrofuran; hexane;
First Step THF (100 ml) was added to <strong>[156573-09-0]1-bromo-4-ethoxy-2,3-difluorobenzene</strong> (5.1 g) in a reaction vessel under an atmosphere of nitrogen, and the mixture was cooled to -78 C. n-Butyllithium (1.57 M, in a hexane solution) (13.8 ml) was added dropwise at a temperature of -70 C. or lower. The stirring was continued at -78 C. for another 2 hours, and 4-(3-propylcyclopentyl)-cyclohexanone (3.0 g) in a THF (10 ml) solution was added dropwise at a temperature of -70 C. or lower. After the mixture had been stirred at -78 C. for another 1 hour, it was warmed to room temperature, and a saturated aqueous solution of ammonium chloride (50 ml) was added. The mixture was separated, and the water layer was extracted with ethyl acetate three times, and then the combined organic layer was washed with brine. The solution was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (eluent: ethyl acetate/n-heptane= 1/9 by volume) to give 1-(4-ethoxy-2,3-difluorophenyl)-4-(3-propylcyclopentyl)cyclohexanol (5.0 g).
With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In Solmix A-11; water; toluene; for 2h;Reflux; Inert atmosphere;
Third Step 4-Bromo-2,3-difluoroethoxybenzene (s-5) (45.2 g), 2, 3-difluorophenyllboronic acid (s-6) (36.1 g), potassium carbonate (79.1 g), Pd (Ph3P)2Cl2 (4.0 g), toluene (200 ml), Solmix A-11 (200 ml) and water (200 ml) were placed in a reaction vessel under an atmosphere of nitrogen, and heated to reflux for 2 hours. After the reaction solution had been cooled to 25C, it was poured into water (200 ml) and toluene (200 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 a mixed solvent of toluene and heptane (toluene: heptane= 2:1 by volume) as an eluent, and further purified by recrystallization from Solmix A-11 and dried to give 4-ethoxy-2,2',3,3'-tetrafluoro-1,1'-biphenyl (s-7) (40.1 g).
With tetrabutylammomium bromide; sodium hydroxide; In water; at 80℃; for 6h;Inert atmosphere;
To an aqueous (400 ml) solution of 4-bromo-2,3-difluorophenol (T-1) (195.0 g), bromoethane (196.2 g) and tetrabutylammonium bromide (hereinafter, abbreviated as TBAB) (24.2 g), sodium hydroxide (75.9 g) was added, and heating agitation was carried out at 80 C for 6 hours in a nitrogen atmosphere. After completion of the reaction, extraction was carried out with heptane, an organic layer was washed with water and a saturated aqueous solution of sodium chloride, and then the resultant solution was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and thus a black oily matter was obtained. The resultant material was purified by distillation, and thus 1-ethoxy-2,3-difluorobromobenzene (T-2) was obtained as a colorless oily matter (230.0 g, yield: 97%).
97%
With tetrabutylammomium bromide; sodium hydroxide; In water; at 80℃; for 6h;Inert atmosphere;
To a water (400 ml) solution of 4-bromo-2,3-difluorophenol (T-1) (195.0 g), bromoethane (196.2 g) and tetrabutylammonium bromide (hereinafter referred to as TBAB) , Sodium hydroxide (75.9 g) were added, and the mixture was heated and stirred at 80 C. for 6 hours under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was extracted with heptane. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a black oil. This product was purified by distillation to give 1-ethoxy-2,3-difluorobromobenzene (T-2) as a colorless oil (230.0 g, yield 97%).
With potassium phosphate; In 1,4-dioxane; for 2h;Reflux; Inert atmosphere;
4-Formylphenylboronic acid (s47) (75.9 g),4-bromo-2,3-difluoroethoxybenzene (s48) (100.0 g), potassium phosphate (269.0g), dichlorobistriphenylphosphinepalladium (II) (Pd(Ph3P)2Cl2;8.9 g) and 1,4-dioxane (500 ml) were placed in a reaction vessel under an atmosphere of nitrogen, and the mixture was heated to reflux for 2 hours. After the reaction mixture had been cooled to 25 C, it 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 product was purified by recrystallization from a mixed solvent of heptane and toluene (heptane:toluene=l: 1 by volume) to give 4-ethoxy-4'-formyl-2,3-difluoro-l,l'-biphenyl (s49) (102.8g). The yield based on the compound (s48) was 92.9%.
trimethyl-(4-ethoxy-2,3-difluorophenylethynyl)silane[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
120 g
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine; In N,N-dimethyl-formamide; at 70℃; for 2h;Inert atmosphere;
Under a nitrogen atmosphere,60 g of trimethylsilylacetylene,120 g of <strong>[156573-09-0]4-ethoxy-2,3-difluorobromobenzene</strong>, 1.9 g of copper iodide,11.7 g of tetrakistriphenylphosphine palladium were dissolved in 500 mL of DMF,And the mixture was stirred at 70 C. for 2 hours.To the reaction mixture were added toluene,Add water,After stirring, the organic layer was separated.The organic layer was washed with waterwater,Ammonia water,Followed by washing with saturated saline in this order,After drying with anhydrous sodium sulfate,The solvent was distilled off under reduced pressure.The obtained crystalRecrystallization and purification by column chromatography (silica gel)120 g of trimethyl- (4-ethoxy-2,3-difluorophenylethynyl) silane was obtained.