* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 2 h; Inert atmosphere Stage #2: With Triisopropyl borate In tetrahydrofuran; hexane at -78 - 20℃; for 17 h; Inert atmosphere Stage #3: With hydrogenchloride In tetrahydrofuran; hexane; water at 20℃; for 1 h;
Under an argon gas atmosphere, a mixture of 212 g (748 mmol) of 2(3-bromophenyl)naphthalene and 3 L of dehydrated TI-IF was cooled down to minus 10 degree C., and 600 ml (948 mmol) of hexane solution of 1.6M n-butyllithium was dropped into the mixture while the mixture was being stirred. Then, the mixture was stirred at 0 degree C. for 2 hours. The reaction solution was again cooled down to minus 78 degrees C., and 450 g (2.39 mol) of triisopropylborate was dropped into the solution. Then, the solution was stirred at room temperature for 17 hours. The reaction mixture was added with aqueous solution of hydrochloric acid and stirred at room temperature for 1 hour. The reaction mixture was added with 3 L of toluene, and aqueous phase thereof was eliminated. After organic phase thereof was dried with magnesium sulfate, the solvent was distilled away under reduced pressure. By recrystallizing the obtained solid by toluene, 126 g of 3-(2-naphthyl)phenylboronic acid was obtained at an yield of 67percent.
50%
Stage #1: With n-butyllithium In diethyl ether; hexane; toluene at -64℃; for 2.5 h; Stage #2: at 20℃; for 12.25 h; Stage #3: With hydrogenchloride; water In diethyl ether; hexane; toluene at 0 - 10℃;
13-B. Preparation of compound 13b; [200] Under N atmosphere, to a compound 13a (4 g, 14.1 mmol) prepared in 13-A, dehydrated ether (80 mL) and dehydrated toluene (80 mL) were added, and cooled to - 640C in ice bath. A 2.5 M butyl lithium/hexane solution (6 mL) was added drop wise thereto for 30 minutes, and subjected to reaction at -640C for 2 hours. Boronic acid triisoester (9 mL) was added dropwise thereto for 15 minutes, and then stirred at room <n="75"/>temperature for 12 hours. After ice cooling, 2 N hydrochloric acid (35 rnL) was added at 1O0C or lower and toluene (10 mL) was added. The mixture was separated, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was re- crystallized from EtOH to prepare a compound 13b (1.75 g, 50percent).
Stage #1: With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In ethanol; water at 50℃; for 4 h; Inert atmosphere Stage #2: With hydrogenchloride In water
General procedure: The procedure for entry v is shown as an example: compound 3 (150 mg,0.228 mmol, tetrahydrate), 2-methoxyphenylboronic acid (139 mg,0.912 mmol), K2CO3 (126 mg, 0.912 mmol), and PdCl2(PPh3)2 (19 mg,0.027 mmol) were placed in a flask under a N2 atmosphere. Degassed EtOH/H2O (5/1; 3 mL) was added, and the reaction mixture was stirred at 50 C for4 h. The solvent was removed under reduced pressure. Hexane/EtOAc (1/1)was added, and the residue was extracted with water. To the aqueous layer,1 M HCl was added dropwise until the pH was approximately 2, and theresulting mixture was extracted twice with EtOAc. The combined organiclayers were dried with Na2SO4 and concentrated in vacuo. The residue waspurified by silica gel column chromatography (hexane/EtOAc = 4/1?1/1) togive 51 mg of the biaryl compound (49percent).
With hydrogenchloride; n-butyllithium In tetrahydrofuran; hexane; toluene
(2) Synthesis of Compound 2-2 Under an argon gas atmosphere, a mixture of 212 g (748 mmol) of 2(3-bromophenyl) naphthalene and 3 L of dehydrated THF was cooled down to -10 degrees C., and added with 600 ml (948 mmol) of hexane solution of 1.6M n-butyllithium in drops while being stirred. Then, the reaction mixture was stirred for two hours at 0 degree C. The reaction solution was further cooled down to -78 degrees C., and added with 450 g (2.39 mol) of triisopropyl borate in drops. Subsequently, the reaction mixture was stirred for 17 hours at room temperature. The reaction mixture was further added with solution of hydrochloric acid to be stirred for one hour at room temperature. The reaction mixture was further added with 3 L of toluene, so that aqueous phase thereof was eliminated. After organic phase thereof was dried with magnesium sulfate, the solvent was distilled away under reduced pressure. By recrystallizing the obtained solid by toluene, 126 g of 3-(2-naphthyl) phenylboronic acid was obtained at an yield of 67percent.
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 9h;Heating / reflux;
2.3 g of 3-(naphthalene-2-yl) phenyl boronic acid prepared by a well known method and 3.8 g of 1-bromo-8-(4-napbthalene-1-yl-phenyl) pyrene were dissolved in 40 ml of DME. Subsequently, 0.19 g of tetrakis(triphenylphosphine)palladium and 13 ml of 2M-sodium carbonate aqueous solution were added therein, followed by argon displacement. After heating and refluxing for 9 hours, it was stood to cool and then an organic layer was extracted therefrom by toluene. The organic layer was washed by saturated salt water, followed by drying through anhydrous sodium sulfate, and then the organic solvent was removed by an evaporator. The residue was refined through a silica gel chromatography (a developing solvent: hexane / toluene = 1 /1) and then 2.7 g of the objective compound (AN-7) was obtained. The measurement result of the compound by FD-MS showed m/z=606 to C48H30 = 606, therefore the objective compound (AN-7) was confirmed (the yield: 58%).
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; for 24h;Heating / reflux;
13-C. Preparation of compound 13c; [202] Under N atmosphere, 9-bromoanthracene (5 g, 19.4 mmol), the compound 5b (4.6 g, 23.3 mmol), Pd(PPh ) (1.1 g, 0.97 mmol) were added to a 2 M aqueous solution of potassium carbonate (30 mL) and THF (300 mL). The mixture was refluxed under stirring for about 24 hours. After completing the reaction, the mixture was cooled to normal temperature. The organic layer was separated from the reaction mixture, dried over magnesium sulfate, and distilled under reduced pressure. The resultant was re- crystallized from THF and EtOH to prepare a compound 13c (5.4 g, 84%). MS [M] = 330
60%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; toluene; at 110℃; for 24h;Inert atmosphere;
9-bromoanthracene (20 g, 78.13 mmol), <strong>[870774-29-1](3-(naphthalen-2-yl)phenyl)boronic acid</strong> (22.3 g, 93.2 mmol), potassium carbonate (21.5 g, 156.3 mmol) were added to a mixture of toluene (600 mL) and water (100 mL) to give a colorless suspension. tetrakis(triphenylphosphine)palladium(0) (2.7 g, 3.9 mmol) was added to the reaction mixture, then the reaction mixture was degassed with nitrogen and heated to 110 C. for 24 hours. After the reaction was cooled down to room temperature, the product was extracted with dichloromethane. The organic phase was separated and collected. The solid was washed with dichloromethane and methanol to afford 9-(3-(naphthalen-2-yl)phenyl)anthracene (18.0 g, 60% yield) as a yellow solid.
Under an argon gas atmosphere, a mixture of 212 g (748 mmol) of <strong>[667940-23-0]2(3-bromophenyl)naphthalene</strong> and 3 L of dehydrated TI-IF was cooled down to minus 10 degree C., and 600 ml (948 mmol) of hexane solution of 1.6M n-butyllithium was dropped into the mixture while the mixture was being stirred. Then, the mixture was stirred at 0 degree C. for 2 hours. The reaction solution was again cooled down to minus 78 degrees C., and 450 g (2.39 mol) of triisopropylborate was dropped into the solution. Then, the solution was stirred at room temperature for 17 hours. The reaction mixture was added with aqueous solution of hydrochloric acid and stirred at room temperature for 1 hour. The reaction mixture was added with 3 L of toluene, and aqueous phase thereof was eliminated. After organic phase thereof was dried with magnesium sulfate, the solvent was distilled away under reduced pressure. By recrystallizing the obtained solid by toluene, 126 g of 3-(2-naphthyl)phenylboronic acid was obtained at an yield of 67%.
50%
13-B. Preparation of compound 13b; [200] Under N atmosphere, to a compound 13a (4 g, 14.1 mmol) prepared in 13-A, dehydrated ether (80 mL) and dehydrated toluene (80 mL) were added, and cooled to - 640C in ice bath. A 2.5 M butyl lithium/hexane solution (6 mL) was added drop wise thereto for 30 minutes, and subjected to reaction at -640C for 2 hours. Boronic acid triisoester (9 mL) was added dropwise thereto for 15 minutes, and then stirred at room <n="75"/>temperature for 12 hours. After ice cooling, 2 N hydrochloric acid (35 rnL) was added at 1O0C or lower and toluene (10 mL) was added. The mixture was separated, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was re- crystallized from EtOH to prepare a compound 13b (1.75 g, 50%).
With hydrogenchloride; n-butyllithium; In tetrahydrofuran; hexane; toluene;
(2) Synthesis of Compound 2-2 Under an argon gas atmosphere, a mixture of 212 g (748 mmol) of 2(3-bromophenyl) naphthalene and 3 L of dehydrated THF was cooled down to -10 degrees C., and added with 600 ml (948 mmol) of hexane solution of 1.6M n-butyllithium in drops while being stirred. Then, the reaction mixture was stirred for two hours at 0 degree C. The reaction solution was further cooled down to -78 degrees C., and added with 450 g (2.39 mol) of triisopropyl borate in drops. Subsequently, the reaction mixture was stirred for 17 hours at room temperature. The reaction mixture was further added with solution of hydrochloric acid to be stirred for one hour at room temperature. The reaction mixture was further added with 3 L of toluene, so that aqueous phase thereof was eliminated. After organic phase thereof was dried with magnesium sulfate, the solvent was distilled away under reduced pressure. By recrystallizing the obtained solid by toluene, 126 g of 3-(2-naphthyl) phenylboronic acid was obtained at an yield of 67%.
General procedure: The procedure for entry v is shown as an example: compound 3 (150 mg,0.228 mmol, tetrahydrate), 2-methoxyphenylboronic acid (139 mg,0.912 mmol), K2CO3 (126 mg, 0.912 mmol), and PdCl2(PPh3)2 (19 mg,0.027 mmol) were placed in a flask under a N2 atmosphere. Degassed EtOH/H2O (5/1; 3 mL) was added, and the reaction mixture was stirred at 50 C for4 h. The solvent was removed under reduced pressure. Hexane/EtOAc (1/1)was added, and the residue was extracted with water. To the aqueous layer,1 M HCl was added dropwise until the pH was approximately 2, and theresulting mixture was extracted twice with EtOAc. The combined organiclayers were dried with Na2SO4 and concentrated in vacuo. The residue waspurified by silica gel column chromatography (hexane/EtOAc = 4/1?1/1) togive 51 mg of the biaryl compound (49%).
With potassium carbonate; In ethanol; water; at 50℃; for 5h;Inert atmosphere;
General procedure: In the zone of the present invention utilizing a stable art type complex of scyllo-inositol as a protecting group, 150 mg (1.10 mmol) of 4-methylphenylboronic acid,324 mg (0.55 mmol) of potassium salt of a stable art type complex of 3-bromophenylboronic acid and scyllo-inositol (0.55 mmol) of potassium salt of scyllo-inositol and 304 mg (2.20 mmol) of potassium carbonate were dissolved in degassed ethanol: 1) mixed solvent, and a catalyst solution prepared by suspending 8 mg (0.012 mmol) of triphenylphosphine ligand-palladium in 1 mL of a mixed solvent of ethanol: water (5: 1) was added thereto , And the cross-coupling reaction was started by stirring at a reaction temperature of 50 C. After 5 hours of reaction, the reaction solvent was distilled off under reduced pressure to stop the reaction. 15 ml of water and 10 ml of ethyl acetate were added to the residue and dissolved / extracted, and the obtained suspension was filtered to remove the insoluble catalyst. Further, an ethyl acetate layer and an aqueous layer were separated, and the aqueous layer was further washed with a small amount of ethyl acetate. The aqueous layer was taken out and hydrochloric acid was added so that the pH became 2 to 3, the scyllo-inositol complex dissociated and the deprotection reaction progressed. The arylboronic acid was insolubilized with deprotection in an acidic aqueous solution. Thereto, 15 ml of ethyl acetate was added to extract the arylboronic acid, and the mixture was separated to obtain an ethyl acetate layer. The aqueous layer was again extracted with 10 ml of ethyl acetate, combined with the first ethyl acetate solution, dried with anhydrous Na 2 SO 4 and concentrated. The precipitated solid was purified by silica gel column chromatography to obtain 177 mg (0.92 mmol) of 4'-biphenyl 3-boronic acid (yield: 84%).
8
[ 870774-29-1 ]
[ 14348-75-5 ]
C45H28O[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In tetrahydrofuran; water; at 65℃;Inert atmosphere;
(2) In a 100 mL three-necked flask, 2-bromofluorenone (2.59 g, 10 mmol), an intermediate (4.47 g, 15 mmol), Cesium carbonate (13.82 g, 30 mmol), 40 mL of tetrahydrofuran and 20 mL of water were added, and PdCl 2 (dppf)-CH 2 Cl 2 (0.16 g, 0.2 mmol) was added under a nitrogen atmosphere, and the temperature was raised to 65 C for 6-24 h. The liquid phase monitoring reaction is completed, cooled to room temperature, filtered, concentrated, and separated by column chromatography. The target compound was obtained in an amount of 3.63 g, yield 84%.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
