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CAS No. : | 1161009-88-6 | MDL No. : | MFCD16660920 |
Formula : | C25H15Br | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | GQXFSXMUBDPXBG-UHFFFAOYSA-N |
M.W : | 395.29 | Pubchem ID : | 68018887 |
Synonyms : |
|
Num. heavy atoms : | 26 |
Num. arom. heavy atoms : | 24 |
Fraction Csp3 : | 0.04 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 0.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 110.44 |
TPSA : | 0.0 Ų |
GI absorption : | Low |
BBB permeant : | No |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | Yes |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -3.69 cm/s |
Log Po/w (iLOGP) : | 3.76 |
Log Po/w (XLOGP3) : | 7.07 |
Log Po/w (WLOGP) : | 6.79 |
Log Po/w (MLOGP) : | 6.66 |
Log Po/w (SILICOS-IT) : | 7.24 |
Consensus Log Po/w : | 6.31 |
Lipinski : | 1.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 1.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -7.43 |
Solubility : | 0.0000148 mg/ml ; 0.0000000373 mol/l |
Class : | Poorly soluble |
Log S (Ali) : | -6.89 |
Solubility : | 0.0000512 mg/ml ; 0.000000129 mol/l |
Class : | Poorly soluble |
Log S (SILICOS-IT) : | -10.98 |
Solubility : | 0.0000000042 mg/ml ; 0.0 mol/l |
Class : | Insoluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 4.0 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In toluene for 16 h; Reflux | a Synthesis of 4-bromos iro-9,9'-bifluorene ( -1) 60 g (152 mmol) 4-bromospiro-9,9'-bifluorene, 47.2 g (182.1 mmol) bis- pinacolatediboron, 3.72 g (4.55 mmol) 1,1'-bis(diphenylphosphino)- ferrocene-palladium(ll)dichloride dichloromethane complex, 44.7 (455 mmol) potassium acetate and 600 ml of toluene is heated under reflux for 16 h. After cooling, 200 ml of water are added, the mixture is stirred for a further 30 min., the organic phase is separated off, filtered through a short Celite bed, and the solvent is then removed in vacuum. The residue is recrystallised several times from heptanes/toluene. Yield: 67.1g, 96percent. |
82.1% | With potassium acetate In 1,4-dioxane at 100℃; for 12 h; Inert atmosphere | Synthesis of Compound 02; The following reagents:dioxane: 140 mL,Compound 01: 7.00 g (17.7 mmol) ,bispinacolatodiboron : 6.75 g (26.6 mmol),potassium acetate: 3.47 g (35.4 mmol), andbis (triphenylphosphine ) palladium ( II ) dichloride: 621 mg(0.885 mmol)were put in a reaction vessel. The reaction solution was stirred at 100°C for 12 hr under a nitrogen atmosphere. It was confirmed by thin layer chromatography that the raw materials disappeared, and instead, a new compound was produced.[0103] The reaction solution was cooled to roomtemperature and was then concentrated under reduced pressure, followed by purification by silica gel column chromatography (eluent: toluene/heptane=l : 1 ) . The target fraction was concentrated, followed by extraction with methanol to obtain 6.43 g (14.5 mmol, yield: 82.1percent) of Compound 02. Theresulting compound was detected as a peak at m/z = 442 by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to confirm being the target compound . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 0.5 h; Stage #2: at -78 - 20℃; for 12 h; |
4-Bromo-9,9'-spirobifluorene (2.5 g, 6.4 mmol) was dissolved in 90 mL of anhydrous THF solution and cooled to -78 °C. Then, 2 M n-BuLi (7 mL,14 mmol) was dropped slowly. After stirring at -78 °C for 30 min, 2-isopropoxy-4,4',5,5'-tetramethyl-[1-3]dioxaborolane (2.75 mL, 14 mmol) was added in one portion. The resulting mixture was stirred for another 12 h and gradually warmed to room temperature. The reaction was quenched with water and extracted with ethyl acetate and water. The organic layer was dried with anhydrous MgSO4 and filtered. The solution was evaporated. Then, the residue was purified by recrystallized from chloroform/ethanolto give a white powder. (2.08 g, Yield 73percent) 1H NMR (300 MHz,DMSO): δ (ppm) 8.72-8.74 (d, 1H), 7.68-7.73 (t, 3H), 7.17-7.25 (q,3H), 6.92-6.97 (t, 4H), 6.56-6.66 (m, 4H), 1.32-1.39 (d, 12H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Compound (1-36-1) (31.6 g, 80 mmol) and 200 mL of anhydrous tetrahydrofuran were added to a 500 mL three-necked flask under nitrogen atmosphere, cooled to -78 C., and 85 mmol of n-butyllithium was slowly added dropwise, the mixture was reacted for 2 hours, then 90 mmol of isopropoxyboronic acid pinacol ester was added one time to allow the reaction temperature to rise to room temperature naturally. The reaction was further performed for 12 hours and then quenched by the addition of pure water. The reaction solution was rotary evaporated to remove most of the solvent, and then extracted with dichloromethane and washed with water for 3 times. The organic phase was collected, spin dried, and then recrystallized, with a yield of 90%. | |
73% | 4-Bromo-9,9'-spirobifluorene (2.5 g, 6.4 mmol) was dissolved in 90 mL of anhydrous THF solution and cooled to -78 C. Then, 2 M n-BuLi (7 mL,14 mmol) was dropped slowly. After stirring at -78 C for 30 min, 2-isopropoxy-4,4',5,5'-tetramethyl-[1-3]dioxaborolane (2.75 mL, 14 mmol) was added in one portion. The resulting mixture was stirred for another 12 h and gradually warmed to room temperature. The reaction was quenched with water and extracted with ethyl acetate and water. The organic layer was dried with anhydrous MgSO4 and filtered. The solution was evaporated. Then, the residue was purified by recrystallized from chloroform/ethanolto give a white powder. (2.08 g, Yield 73%) 1H NMR (300 MHz,DMSO): delta (ppm) 8.72-8.74 (d, 1H), 7.68-7.73 (t, 3H), 7.17-7.25 (q,3H), 6.92-6.97 (t, 4H), 6.56-6.66 (m, 4H), 1.32-1.39 (d, 12H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With hydrogenchloride; acetic acid; In water; for 12h;Reflux; | 9-(2?-bromobiphenyl-2-yl)-9H-fluoren-9-ol (36 g, 94 mmol) was dissolved in a mixture of acetic acid (360 mE) and hydrochloric acid (36 mE, 3 6%). The mixture was refluxed and stirred for 12 hours. After removing the solvent, the silica-gel column was performed such that 4-bromo-9, 9?-spirobi[fluorene] was obtained. (32 g, yield: 86%) |
175 g | With toluene-4-sulfonic acid; acetic acid; for 2h;Inert atmosphere; Reflux; | Argon under the protection,To a 3 L three-necked flask was added 210 g of 1 - (2'-bromo- [1,1'-biphenyl] -2-yl) -9-fluorenol and 1 L of glacial acetic acid,3 g of p-toluenesulfonic acid was added to the reaction and heated to reflux for 2 h,After cooling to room temperature, the mixture was filtered to give a white solid,Methanol washing,dry,To give 175 g of 4-bromo-9,9 spirobifluorene(Compound 2, content 97.5%, impurity 4-iodo-9,9'-spirobifluorene content 0.6%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In toluene; for 16h;Reflux; | a Synthesis of 4-bromos iro-9,9'-bifluorene ( -1) 60 g (152 mmol) 4-bromospiro-9,9'-bifluorene, 47.2 g (182.1 mmol) bis- pinacolatediboron, 3.72 g (4.55 mmol) 1,1'-bis(diphenylphosphino)- ferrocene-palladium(ll)dichloride dichloromethane complex, 44.7 (455 mmol) potassium acetate and 600 ml of toluene is heated under reflux for 16 h. After cooling, 200 ml of water are added, the mixture is stirred for a further 30 min., the organic phase is separated off, filtered through a short Celite bed, and the solvent is then removed in vacuum. The residue is recrystallised several times from heptanes/toluene. Yield: 67.1g, 96%. |
82.1% | With potassium acetate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; at 100℃; for 12h;Inert atmosphere; | Synthesis of Compound 02; The following reagents:dioxane: 140 mL,Compound 01: 7.00 g (17.7 mmol) ,bispinacolatodiboron : 6.75 g (26.6 mmol),potassium acetate: 3.47 g (35.4 mmol), andbis (triphenylphosphine ) palladium ( II ) dichloride: 621 mg(0.885 mmol)were put in a reaction vessel. The reaction solution was stirred at 100C for 12 hr under a nitrogen atmosphere. It was confirmed by thin layer chromatography that the raw materials disappeared, and instead, a new compound was produced.[0103] The reaction solution was cooled to roomtemperature and was then concentrated under reduced pressure, followed by purification by silica gel column chromatography (eluent: toluene/heptane=l : 1 ) . The target fraction was concentrated, followed by extraction with methanol to obtain 6.43 g (14.5 mmol, yield: 82.1%) of Compound 02. Theresulting compound was detected as a peak at m/z = 442 by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to confirm being the target compound . |
71% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 120℃; | 4-bromo-9,9'-spirobi [fluorene] (50.0 g, 126 mmol) was dissolved in DMF (632 mL), followed by bis (pinacolato) diboron (35.3 g, 139 mmol), KOAc (37.2 g, 379 mmol) ), PdCl 2 (dppf) (2.78 g, 3.79 mmol) was added and stirred at 120 C. When the reaction is complete, DMF is removed by distillation and extracted with CH 2 Cl 2 and water. After extraction is completed, the organic layer is dried over MgSO 4 and concentrated. Thereafter, the resulting compound was recrystallized after applying a silica gel column to obtain 39.7 g (yield: 71%) of the product. |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; palladium diacetate; In toluene; for 16h;Reflux; | The obtained bromide B-1 (7.89 g, 20 mmol), pinacol borate (6.22 g, 24 mmol), 1,1'-bis(diphenylphosphino)-ferrocene-palladium dichloride (II) Dichloromethane complex (0.49 g, 0.6 mmol), potassium acetate (5.90 g, 60 mmol) and 79 ml of toluene were reacted under reflux for 16 hours, cooled, added with 26 ml of water, stirred for 30 minutes, and the organic phase was separated and passed. The celite bed was filtered, and then the organic solvent was evaporated, and the obtained crude product was recrystallized from heptane/toluene. The obtained solid (6.64 g, 15 mmol), p-bromoiodobenzene (4.05 g, 14.3 mmol), Tetrakis(triphenylphosphine)palladium (0.35 g, 0.3 mmol), toluene (43 ml),Aqueous sodium carbonate (2M, 21 ml) was added to the flask, and the mixture was refluxed for 8 hours and then cooled to room temperature.It is extracted with toluene, and the organic phase is washed with brine, and then dried, and then purified by column chromatography.Bromide B-42 was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With hydrogenchloride; acetic acid; In water; for 1h;Reflux; | After the intermediate F was dissolved in acetic acid to complete the addition of concentrated hydrochloric acid and the reaction for 1 hour under reflux. It was extracted using ether and water and the organic layer was washed with mwot Sat NaHCO3. The organic layer was dried over MgSO4 column chromatography and recrystallization to give the intermediate G (yield: 84%). |
77% | With acetic acid; at 100℃; for 12h; | Under the protection of argon, 10 mmol of 4-bromofluorenone was added to the reaction flask.11mmol of 2-fluorobiphenyl and 20ml of tetrahydrofuran solvent, after stirring evenly,22 mmol of lithium metal tablets were added to the reaction solution in batches.Then, the temperature is raised to about 60 C, and the reaction is carried out for 12 hours.After the reaction was completed and returned to room temperature, the reaction was quenched with 20 mL of 1N aqueous hydrochloric acid.The organic phase was separated, and the tetrahydrofuran was evaporated to dryness on a rotary evaporator.The crude solid was added to 10 ml of acetic acid.Heat to 100 C for 12 hours.After the completion of the ring closure reaction, filtration was carried out to give 4-bromo-9,9'-spirobifluorene as a crude product.The crude product uses a mixed solvent of dichloromethane and n-hexane as an eluent.Perform column chromatography separation, and the chromatographic silica gel is 200-300 mesh.Finally, the product 4-bromo-9,9'-spirobifluorene 3.04g was obtained.The yield was 77%. |
With hydrogenchloride; acetic acid; In water; at 120℃; for 1.16667h; | Example 1; Synthesis of Example Compound D01; Synthesis of Compound 01; A Grignard reagent was prepared by putting 1.5 g (61.8 mmol) of magnesium in a reaction vessel, replacing the atmosphere inside the reaction vessel with argon, and then dropping 11.7 g (50.2 mmol) of 2-bromobiphenyl dissolved in 55 mL of dehydrated diethyl ether into the reaction vessel with stirring.[0098] The following reagent and solvent: dehydrated diethyl ether: 50 mL, and2-bromofluorenone : 10 g (38.6 mmol)were put in another reaction vessel. The Grignard reagent prepared in advance was dropped into this reaction vessel, followed by stirring for 30 min. It was confirmed by thin layer chromatography that the raw materials disappeared, and instead, a new compound was produced.[0099] The reaction solution was cooled to 0C and was subjected to extraction with a saturated ammonium chloride aqueous solution and ethyl acetate, and the organic layer was collected. After drying with sodium sulfate, the solvent was distilled off to obtain an intermediate of Compound 01.[0100] The intermediate of Compound 01 and 200 mL of acetic acid were put in another reaction vessel. This reaction solution was heated to 120C, and 20 mL ofconcentrated hydrochloric acid was dropped thereto over 10 min with stirring, followed by stirring at 120C for 1 hr. It was confirmed by thin layer chromatography that the raw materials disappeared, and instead, a new compound was produced.[0101] The reaction vessel was cooled to 0C, and the precipitate was collected and was washed with water and ethanol to obtain 13.0 g (33.1 mmol, yield: 85.8%) ofCompound 01. The resulting compound was detected as a peak at m/z = 394 by gas chromatography-mass spectrometer (GS-MS) and was thereby confirmed to be the target compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | At -78 C under argon with 318mL n-BuLi (in hexane 2.5M, 785mmol)2,2'-dibromobiphenyl(250g, 785mmol) in THF (1900ml) was added.The mixture was stirred for 30 minutes. Was added dropwise 9-one (144g, 785mmol) in 1000mLTHF added. The reaction was carried out at -78 C for 30 minutes and then stirred at room temperature and Stirred overnight. The reaction was quenched with water, and the solid was filtered. Without further purification,Said alcohol (299g, 92%), acetic acid (2200mL) and concentrated HCl (100mL) mixed .It was refluxed for 2 hours. After cooling, the mixture was filtered and washed with water and vacuum dry. The product was isolated as a white solid (280g, 98% of theory). | |
98% | A solution of 2,2?-dibromo-biphenyl (250 g, 785 mmol) in THF (1900 ml) is treated with 318 mL of n-BuLi (2.5 M in hexane, 785 mmol) under argon at -78 C. The mixture is stirred for 30 minutes. A solution of Fluoren-9-one (144 g, 785 mmol) in 1000 mL THF is added dropwise. The reaction proceeds at -78 C. for 30 minutes and then is stirred at room temperature overnight. The reaction is quenched with water and the solid is filtered. Without further purification, a mixture of the alcohol (299 g, 92%), acetic acid (2200 mL) and concentrated HCl (100 mL) is refluxed for 2 hours. After cooling, the mixture is filtered and washed with water and dried under vacuum. The product is isolated in the form of a white solid (280 g, 98% of theory). | |
90% | 1a) Synthesis of 4-bromospiro-9,9'-bifluorene 60 g ( 188.5 mmol) 2,2'-Dibromo-biphenyl (CAS 13029-09-9) is dissolved in 750 mL of dry THF and cooled down to -78C. 75.4 mL (188.5 mmol) of a 2.5M solution of nBuLi in heptane is added dropwise. After 1h a solution of 34.6 g of fluorenone (188.5 mmol) (CAS 486-25-9) in 250 mL of THF is added dropwise. The reaction mixture is allowed to reach the room temperature overnight, then quenched with saturated NH4CI (100 mL) solution, the mixture is stirred briefly, the organic phase is separated off, and the solvent is removed in vacuum. The residue is suspended in 500 ml of glacial acetic acid at 40C, 0.5 ml of cone, hydrochloric acid is added to the suspension, and the mixture is subsequently stirred at 100C for a further 2 h. After cooling, the precipitated solid is filtered off with suction, washed once with 100 ml of glacial acetic acid, three times with 100 ml of ethanol each time and finally recrystallized from dioxane. Yield: 70.1 g (169 mmol), 90%; purity about 98% according to 1H-NMR. |
50% | 2,2'-Dibromobiphenyl (4.25 g, 13.6 mmol) was dissolved in70 mL of anhydrous THF solution and cooled to -78 C. Then, 1.6 Mn-BuLi (9.4 mL) was added dropwise slowly. The whole solutionwas stirred at -78 C for 30 min, followed by addition of a solutionof 9H-fluorene-9-one (2.94 g, 16.3 mmol) in 20 mL of anhydrousTHF under N2 atmosphere. The solution was gradually warmed toroom temperature and quenched by saturated, aqueous NaHCO3(30 mL). The solution was extracted with dichloromethane andwater. The organic layer was dried with anhydrous MgSO4, filtered,and evaporated. The crude product was purified by column chromatographyon silica gel using 1:1 dichloromethane/hexane. Thewhite powdery product was placed in other two-necked flask, anddissolved in acetic acid (100 mL). Catalytic amount of aqueous HCl (9 mL) was then added and the whole solution was refluxed for12 h. After cooling to ambient temperature, purification by columnchromatography on silica gel using 1:5 dichloromethane/hexane asan eluent gave a white powder. (2.63 g, Yield 50%) 1H NMR(300 MHz, CDCl3): delta (ppm) 8.6 (d, 1H), 7.82-7.85 (d, 2H), 7.52 (d,1H), 7.34-7.50 (m, 3H), 7.09-7.19 (m, 3H), 6.91-6.96 (t, 1H), 6.71-6.74 (d, 3H), 6.64-6.67 (d, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In N,N-dimethyl-formamide; at 150℃; | General procedure: 9,9'-Spirobi[fluorene] brominated compound, boronic acid compound, K2CO3 and Pd(dppf)Cl2 were dissolved in dry DMF or xylenes. The mixture was warmed to 150 C (DMF) and 135 C (xylenes) stirred overnight. After cooling to room temperature, saturated solution of ammonium chloride (50 mL) was added, and organic layer was extracted three times with dichloromethane (3x30 mL) and washed with brine (3x30 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using Teledyne Isco CombiFlash Rf 400. Column conditions can be found in each compounds description below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In N,N-dimethyl-formamide; at 150℃; | General procedure: 9,9'-Spirobi[fluorene] brominated compound, boronic acid compound, K2CO3 and Pd(dppf)Cl2 were dissolved in dry DMF or xylenes. The mixture was warmed to 150 C (DMF) and 135 C (xylenes) stirred overnight. After cooling to room temperature, saturated solution of ammonium chloride (50 mL) was added, and organic layer was extracted three times with dichloromethane (3x30 mL) and washed with brine (3x30 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using Teledyne Isco CombiFlash Rf 400. Column conditions can be found in each compounds description below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | General procedure: At -78 C under argon with 318mL n-BuLi (in hexane 2.5M, 785mmol)2,2'-dibromobiphenyl(250g, 785mmol) in THF (1900ml) was added.The mixture was stirred for 30 minutes. Was added dropwise 9-one (144g, 785mmol) in 1000mLTHF added. The reaction was carried out at -78 C for 30 minutes and then stirred at room temperature and Stirred overnight. The reaction was quenched with water, and the solid was filtered. Without further purification,Said alcohol (299g, 92%), acetic acid (2200mL) and concentrated HCl (100mL) mixed .It was refluxed for 2 hours. After cooling, the mixture was filtered and washed with water and vacuum dry. The product was isolated as a white solid (280g, 98% of theory). | |
90% | General procedure: Grignard reagent corresponding to a 2.7 g (110 mmol) of iodo-activated magnesium turnings and 25.6 g (110 mmol) of 2-bromo-phenyl mobayi, 0.8 ml of 1,2-dichloroethane, 50 ml of 1,2 -dimethoxy-ethane, is prepared from a mixture of 400 ml of toluene and 200 ml of THF, and the secondary heating using an oil bath at 70 . When the magnesium is completely reacted, and the reaction mixture was allowed to cool the mixture to room temperature, it was added dropwise after the solution of 1-bromo-fluorenone [36804-63-4] in 25.9 g (100 mmol) in 500 ml of THF, and the reaction mixture 4 after heating at 50 for h, and stirred at room temperature for a further 12 h. It was added to 100 ml of water, and to put the mixture was stirred briefly, and the organic phase was separated, the solvent was removed under vacuum. And the residue was suspended in glacial acetic acid in 500 ml of lukewarm 40 , it was added to the suspension and 0.5 ml of concentrated sulfuric acid, subsequently the mixture is stirred for a further 2 h at 100 . After cooling, the precipitated solid by suction filtrationOut, the screen washed once with 100 ml of glacial acetic acid and washed three times with 100 ml of ethanol each time, and finally recrystallized from dioxane. Yield: 26.9 g (68 mmol), 68%; purity about 98% according to 1H-NMR. | |
90% | General procedure: A solution of 2,2?-dibromo-biphenyl (250 g, 785 mmol) in THF (1900 ml) is treated with 318 mL of n-BuLi (2.5 M in hexane, 785 mmol) under argon at -78 C. The mixture is stirred for 30 minutes. A solution of Fluoren-9-one (144 g, 785 mmol) in 1000 mL THF is added dropwise. The reaction proceeds at -78 C. for 30 minutes and then is stirred at room temperature overnight. The reaction is quenched with water and the solid is filtered. Without further purification, a mixture of the alcohol (299 g, 92%), acetic acid (2200 mL) and concentrated HCl (100 mL) is refluxed for 2 hours. After cooling, the mixture is filtered and washed with water and dried under vacuum. The product is isolated in the form of a white solid (280 g, 98% of theory). |
With sulfuric acid; acetic acid;Reflux; | General procedure: Compound B 1 (20 g, 44.84 mmol) was added to acetic acid (250 ml), 2 ml of sulfuric acid was added dropwise, and the mixture was refluxed with stirring. Temperature to room temperatureAnd neutralized with water. The filtered solid was recrystallized from ethyl acetate to obtain Compound C1 (13.43 g, 70%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With rubidium carbonate; tri-tert-butyl phosphine; palladium diacetate; In 5,5-dimethyl-1,3-cyclohexadiene; for 24h;Reflux; | 4-bromo-spiro-9,9'-spirobifluorene , <strong>[56525-79-2]3,6-diphenyl-9-H-carbazole</strong> and 29. 2g Rb2CO3 suspended in 250mL of xylene. To the suspension to provide 0. 95g (4. 2mmol) Pd(OAc) 2 and 12. 6ml 1M The butylphosphine solution. The mixture was stirred under reflux for 24 hours. After cooling, the organic phase was separated,150mL of water three times, and then concentrated to dryness in vacuo. The residue was extracted with hot toluene, recrystallized three times from toluene,Then sublimation under high vacuum. The yield was 19. 6g (30. 9mmol), corresponding to 66percent of the theoretical value. Purity according to HPLCIt was 99.9percent. |
66% | With rubidium carbonate; tri-tert-butyl phosphine; palladium diacetate; In para-xylene; for 24h;Reflux; | 19.2 g (47 mmol) 4-Brom-9-spirobifluorene, 15 g (47 mmol) 3,6-Diphenyl-9-H-carbazole and 29.2 g Rb2CO3 are suspended in 250 mL p-Xylol. To the suspension are given 0.95 g (4.2 mmol) Pd(OAc)2 and 12.6 ml of a 1M solution of Tri-tert-butylphosphine. The mixture is stirred 24 h under reflux. After cooling the organic phase is separated, washed three times with 150 mL water and is subsequently concentrated to dryness in vacuo. The residue is hot extracted with toluene, recrystallized three times from toluene and subsequently sublimated at high vacuum. Yield is 19.6 g (30.9 mmol) corresponding to 66percent of theory. Purity is according to HPLC 99.9percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; for 2h;Reflux; Inert atmosphere; | To biphenyl-2-yl - (9,9-dimethyl-9H- fluoren-2-yl) amine (40.0g, lllmmol) and4-bromo -9, 9 '- spirobifluorene (56. 9g, 144mmol) in degassed toluene (500ml) was added tri-t-butylphosphine(4 · 4ml 1. 0M in toluene solution, 4 · 4mmol), palladium acetate (248mg, 1. Lmmol) and sodium tert-butoxide (16. 0g,166mmol), and the mixture was heated at reflux for 2 hours. The reaction mixture was cooled to room temperature, toluene expansion and siliconDiatomaceous earth filtration. The filtrate was evaporated in vacuo, and the residue from ethyl acetate / heptane recrystallization. Soxhlet extractor (ABenzene) to extract the crude product and by region in a vacuum sublimation (P = 3X10 4 mbar, Tau = 298 C) was purified twice.Separating the product as a pale yellow solid (20. 4g, 27% of theory, purity according to HPLC> 99.99%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | With (bis(tricyclohexyl)phosphine)palladium(II) dichloride; cesium fluoride; In toluene; for 12h;Inert atmosphere; | <strong>[1161009-88-6]4-bromo-spiro-9,9'-spirobifluorene</strong> and 9,9-dimethyl-N-(4-phenylphenyl)-N-[4-(4,4,5,5 tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-9H-fluoren-2-amine PdCl2 (Cy) 3,15g (99mmol) of cesium fluoride was dissolved in 500mL of toluene. The reaction mixture was refluxed under an argon atmosphere And stirred for 12 hours, and after cooling to room temperature, the mixture was filtered through celite. The filtrate was evaporated in a vacuum, and soThe residue was crystallized from heptane. The crude product was extracted in a Soxhlet extractor (toluene), and in a vacuum and purified by zone sublimationtwice. Isolated as a pale yellow solid product (9g, 24% of theory, by HPLC purity> 99.99%). |
24% | With cesium fluoride; In toluene; for 12h;Inert atmosphere; Reflux; | 28 g (49.4 mmol) of Biphenyl-4-yl-(9,9-dimethyl-9H-fluoren-2-yl(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]amine, 20 g (49.4 mmol) of 4-bromspirobifluorene, 1.8 g (2.5 mmol) of PdCl2(Cy)3, 15 g (99 mmol) of cesium fluoride are dissolved in 500 mL of toluene. The reaction mixture is refluxed and agitated under an argon atmosphere for 12 hours and after cooling to room temperature, the mixture is filtered through Celite. The filtrate is evaporated in vacuo, and the residue is crystallised from heptane. The crude product is extracted in a Soxhlet extractor (toluene) and purified by zone sublimation in vacuo twice. The product is isolated in the form of a pale-yellow solid (9 g, 24% of theory, purity >99.99% according to HPLC). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; palladium diacetate; sodium t-butanolate; In toluene; for 5h;Reflux; | 54 g (137 mmol) of 4-Wibro MOS fatigue -9, 9'-by aminofluorene (1161009-88-6), 17.9 g (140 mmol) of 2-chloroaniline, 68.2 g (710 mmol) sodium tert-butoxide, 613 mg (3 mmol) 3.03 g (5 mmol) acetate and (II) its optical isomer or pharmaceutically acceptable salt of a dissolving the of the toluene 1.3 l dppf, in the reflux during 5 h stirring section. Reaction mixture cooled to room temperature and, the (extend) extender in toluene, the filtering through a BTS plates comprises a back plate supply unit. Filtrate under vacuum and evaporating, was used to determined from heptane with a toluene/residue. Adaptation is isolated as a solid colorless product. Yield: 52.2 g (118 mmol), 86% theory. The compound is similarly is produced: |
86% | With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; sodium t-butanolate; In toluene; for 5h;Reflux; | Example 2a Synthesis of (2-chlorophenyl)(spiro-9,9'-bifluoren-4-yl)amine 54.1 g (137 mmol) of 4-bromospiro-9,9'-bifluorene [1161009-88-6], 17.9 g (140 mmol) of 2-chloroaniline [95-51-2], 68.2 g (710 mmol) of sodium tertbutoxide, 613 mg (2.7 mmol) of palladium(II) acetate and 3.03 g (5.5 mmol) of 1,1'-bis(diphenylphosphino)ferrocene are initially introduced in 1300 ml of toluene and heated under reflux for 5 hours. After cooling to room temperature, the reaction mixture is extended with 700 ml of toluene and filtered through Celite. The solvent is removed in a rotary evaporator, and the residue is recrystallised from a toluene/heptane mixture (1:2). Drying in vacuo leaves 52.2 g (118 mmol, 86% of theory) of the product as a pale-yellow solid. |
58% | With palladium diacetate; sodium t-butanolate; XPhos; In o-xylene; for 8h;Reflux; | 4-bromo-9,9'-spirobifluorene (20 g, 51 mmol), 2-chloroaniline (10 g, 76 mmol), sodium tert-butoxide (10 g, 102 mmol), palladium acetate (0.5 g), X (1g) and o-xylene (200 ml) were heated under reflux for 8 hours. The inorganic material was removed by hot filtration, cooled and concentrated. The crude product was purified by column chromatography to give 13 g of product in 58% yield. |
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; sodium t-butanolate; In toluene; for 5h;Reflux; | 54 g (137 mmol) of <strong>[1161009-88-6]4-bromo-9,9'-spirobi[fluorene]</strong>, 17.9 g (140 mmol) of 2-chloroaniline, 68.2 g (710 mmol) of sodium tertbutoxide, 613 mg (3 mmol) of palladium(II) acetate and 3.03 g (5 mmol) dppf was dissolved in 1.3 l of toluene, and the mixture was stirred under reflux for 5 h. The reaction mixture was cooled to room temperature, extracted with toluene and filtered over Celite. The filtrate was evaporated in vacuo and the residue was crystallised from toluene /hexane. The product is isolated as a colorless solid. Yield: 52.2 g (118 mmol), theoretical yield 86%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | General procedure: 100 millimoles of monobromide or 50 millimoles of the dibromide or 33 millimoles of dibromide or 25 mmol of tetrabromides in 1000 ml THF was cooled to -78 C and stirred , in order to make the temperature of not more than -55 C and added dropwise 105 mmol of the n-BuLi in 2.5M-hexane solution. After the end of addition, the mixture is stirred in addition 2 hours, and when the temperature is not more than -55 C and added dropwise 110 millimoles of fluoroalkyl borane in 200mL THF solution. The mixture is then stirred at -78 C for 1h and gradually warmed to room temperature. Add 50 ml after methanol, substantially under reduced pressure to remove the solvent, the residue is dissolved in 500 ml methylene chloride, organic reinforced with each 200 ml of water and washing five times 200 ml wash once with saturated sodium chloride solution, then after magnesium sulfate drying. The residue obtained after removal of solvent by repeating the recrystallization (for example from toluene, acetone, ethyl acetate and ol such as methanol, ethanol, isopropanol, etc. combination) to purify, and finally in a high vacuum (p is about 10 -5 to 10 -6 mbar, T is about 250-400 C) hierarchical sublimation of the two. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | 250g(785 mmol)of 2,2'-dibromobiphenyl in 2000mL THF was stirred and cooled to -78 C and added dropwise 2.5M n-BuLi in n-hexane solution of 318mL, and the mixture was stirred for another 30 minutes. After adding dropwise 144g (785 mmol) of fluorene in 1000mL THF solution, and the mixture was stirred for an additional 30 minutes and the mixture was allowed to warm to room temperature overnight. The solvent was removed under reduced pressure and the residue was dissolved in glacial acetic acid 2000mL. Added 200mL of EtOH and 1 OOmL of concentrated hydrochloric acid and the mixture was heated at reflux for 2 hours. After cooling, the use of pumpingThe precipitated solid was suction filtered and washed twice each 500mL glacial acetic acid and then washed three times with each 300mL ethanol, andDried under reduced pressure. Yield: 265g (667 mmol) 85%. According to NMR purity of about 98%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; for 6h;Reflux; | The compound (11) 0.50 g (1.08 mmol) and 4- bromo -9,9'- spiro rate [fluorene] (4-bromo-9,9'-spirobi(fluorene)) 0.35 g (0.98 mmol) were melted in the toluene 5 mLand ethanol 2 mL and the tetrakis triphenylphosphine palladium 0.033 g (0.029 mmol) and 2M potassium carbonate aqueous solution 1.5 mL were added and it mixedreflux for 6 hours. The precipitate which was the reaction mixture generated after doing the cooling in a roomtemperature was filtered after decompression and it washed with toluene, water, and the methanol. After thefiltered precipitate was melted in chloroform and it recrystallized as the methanol and it filtered the major product was separated according to the column chromatography (ethyl acetate / normal hexane 1:3) and the compound ( 3-20, and the mks- 4-33 ) 0.26 g (yield 36%)were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 110℃; for 6h; | An intermediate G with the intermediate P by each injection and 1mol Pd2dba3, t-Bu3P, t-BuONa, toluene was stirred into each of the next 6 hours at 110 C. When the reaction is complete remove the cooling, the temperature of the reaction to room temperature, a small amount of water in the organic layer was extracted using CH2Cl2 and water over anhydrous MgSO4, and then filtered under reduced pressure, to the compounds produced by concentrating the organic solvent was purified by column chromatography and recrystallization to give the desired compound 12 (yield: 74%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Intermediate G was dissolved in anhydrous THF, cooled to -78 of reaction, after the n-BuLi was added dropwise slowly, and the reaction was stirred for 1 hour at 0 . Thereafter, the lower the temperature of the reaction to -78 added dropwise trimethyl borate, and stirred at room temperature for 12 hours after. After the reaction was completed into a 2N-HCl aqueous solution, extracted with ether, then stirred for 30 minutes.Removing water in the organic layer over anhydrous MgSO4 and then filtered under reduced pressure, concentrate the organic solvent and column chromatography and the resulting compound to recrystallization to obtain the desired intermediate H (yield: 81%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With palladium diacetate; sodium t-butanolate; CyJohnPhos; In o-xylene;Reflux; Inert atmosphere; | A mixture of 19.8 g(50 mmol) 4-bromo-9,9?-spirobi[fluorene], 9.3 g(55 mmol) of biphenyl-2-amine, 0.25 g(1 mmol) of palladium(II)acetate, 0.75 g(2.0 mmol) of 2-(dicyclohexylphosphino)biphenyl, 9.6 g(100 mmol)of sodium tert-butoxide and 100 ml of o-xylene was refluxed under nitrogen overnight. After finishing the reaction, the solution was filtered at 100 C., to receive the filtrate, and the filtrate was added to 1 L MeOH, while stirring and the precipitated product was filtered off with suction. To give 12.3 g(yield 51%) of yellow product which was recrystallized from hexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; sodium t-butanolate; In toluene; for 20h;Reflux; | 1 ,1 '-Bis(diphenylphosphino)ferrocene (0.83 g, 1.49 mmol), palladium acetate (0.34 mg, 1.49 mmol) and sodium tert-butoxide (9.3 g, 97.1 mmol) are added to a solution of fluoren-2-yl-amine (15.6 g, 97.1 mmol) and 4-bromo-9,9-spiro-bifluorene (30.0 g, 97.1 mmol) in degassed toluene (500 ml), and the mixture is heated under reflux for 20 h. The reaction mixture is cooled to room temperature, extended with toluene and filtered through Celite. The filtrate is extended with water, re-extracted with toluene, and the combined organic phases are dried and evaporated in vacuo. The residue is filtered through silica gel (heptane/dichloromethane) and crystallised from heptane/toluene. (9,9-dimethyl-9H-fluoren-2-yl)-(9,9- spirobifluoren-4-yl)-amine is obtained as a off-white solid (36.0 g, 92% of theory). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; for 2h;Reflux; | Tri-tert-butyiphosphine (1.69 ml of a 1.0 M solution in toluene, 1.69 mmol), palladium acetate (190 mg, 0.85 mmol) and sodium tert-butoxide (9.7 g, 01.4 mmol) are added to a solution of (9,9-dimethyl-9H-fluoren-2-yl)-(9,9- spirobifluoren-4-yl)-amine (18.0 g, 33.8 mmol) and 4-bromo-9,9'- spirobifluorene (13.6g, 33.8 mmol) in degassed toluene (400 ml), and the mixture is heated under reflux for 2 h. The reaction mixture is cooled to room temperature, extended with toluene and filtered through Celite. The filtrate is evaporated in vacuo, and the residue is crystallised from toluene/heptane. The crude product is extracted in a Soxhlet extractor (toluene) and purified by zone sublimation in vacuo twice. The product is isolated in the form of a white solid (19.8 g, 70% of theory, purity > 99.99% according to HPLC). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; for 2h;Reflux; Inert atmosphere; | Tri-tert-butylphosphine (4.4 ml of a 1.0 M solution in toluene, 4.4 mmol),palladium acetate (248 mg, 1.1 mmol) and sodium tert-butoxide (16.0 g,166 mmol) are added to a solution of phenyl-(9,9-dimethyl-9H-fluoren-2- yl)amine (40.0 g, 140 mmol) and 4-bromo-9,9?-spirobifluorene (56.9 g, 144 mmol) in degassed toluene (500 ml), and the mixture is heated under reflux for 2 h. The reaction mixture is cooled to room temperature,extended with toluene and filtered through Celite. The filtrate is evaporated in vacuo, and the residue is crystallised from ethyl acetate/heptane. The crude product is extracted in a Soxhlet extractor (toluene) and purified by zone sublimation in vacuo twice (p = 3 x 10 mbar, T = 298C). The prod-uct is isolated in the form of a pale-yellow solid (20.4 g, 24% of theory, purity> 99.99% according to HPLC). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
141.7 g | Under argon, 175 g of compound 2 and 500 mL of tetrahydrofuran were added to a 5 L three-necked flask,2.2 mol (506.33 g) of tributyl borate was added,Down to -60 C,2.2 mol (880 mL) of 2.5 mol / L n-butyllithium was slowly added dropwise,After the reaction was complete for 4 hours,The reaction ends,3mo 1 aqueous solution of ammonium chloride hydrolysis,Separate the organic layer,Saturated sodium chloride aqueous solution After washing the organic layer,300 g of anhydrous magnesium sulfate for 5 h,Filtration to obtain a pale yellow liquid,The solvent was recovered under reduced pressure to give an off-white solid.500 mL of chloroform and 1 L of petroleum ether to give the desired product 9,9'-spirobifluorene-4-boronic acid (Compound 3)After vacuum drying at 60 C for 5 h, 141.7 g of a white solid was obtained with a total yield of 78.3%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; for 8h;Reflux; | To the flask was added 4-bromo-9,9'-spirobifluorene (15 g, 38 mmol)O-nitrophenyl boronic acid (6.4g, 38mmol),Potassium carbonate (10.4 g, 76 mmol),Tetraphenylphenylpalladium (0.5 g),Tetrahydrofuran (200 ml) and water (100 ml)Heated to reflux for 8 hours,cool down,concentrate,Extracted with dichloromethane,dry,concentrate,The crude product was purified by column chromatography to give 15 g of product,Yield 90%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; for 12h;Reflux; Inert atmosphere; | 49 g (320 mmol) of 4-chioro-phenylboronic acid, 120 g (304 mmol) of 4-bromo-spirobifluorene, 3.51 g (3.04 mmol) of Pd(PPh3)4, 122 g (1 mol) of potasium carbonate are dissolved in 700 mL of toluene. The reaction mixture is refluxed and stirred under an argonatmosphere for 12 hours and after cooling to room temperature, the mixture is filtered through Celite. The filtrate is evaporated in vacuo, and the residue is crystallised from heptane. The product is isolated in the form of a white solid (110 g, 85% of theory). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; for 3h;Reflux; | Tri-tert-butylphosphine (2.5 ml of a 1.0 M solution in toluene, 2.5 mmol),palladium acetate (284 mg, 1.26 mmol) and sodium tert-butoxide (9.12g, 95mmol) are added to a solution of biphenyl-4-yl-[1,1?;3?,1?]terphenyl-4?-yl- amine (25.2 g, 63 mmol) and 4-bromo-9,9?-spirobifluorene (25 g, 63 mmol) in degassed toluene (500 ml), and the mixture is heated under reflux for 3 h. The reaction mixture is cooled to room temperature, diluted with touene andfiltered through Celite. The filtrate is evaporated in vacuo, and the residue iscrystallised from toluene/heptane. The crude product is extracted in a Soxhlet extractor (toluene) and purified by recrystallization in heptane/toluene (23 g, 51% of theory). After sublimation in vacuo, the prod15 uct is isolated in the form of an off-white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 24h;Reflux; | 4.5 g (12.1 mM) of Compound 6-3-1, 5.7 g (14.5 mM) of 4-bromo-9,9'-spirobifluorene, Pd (PPh3) 4 699 mg (0.625 mM), K2CO3 3.34 g (24.2 mM) was dissolved in toluene / ethanol / water 100/20/20 mL and refluxed for 24 hours. After completion of the reaction, distillation at room temperature The organic layer was dried over MgSO4 and the solvent was removed by rotary evaporator. The reactants The residue was purified by chromatography (DCM: Hex = 1: 3) and recrystallized from methanol to obtain 5.7 g (75%) of the desired compound 177. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 24h;Reflux; | A mixture of 4.5 g (12.1 mM) of Compound 1-3-1, 5.7 g (14.5 mM) of 4-bromo-9,9'-spirobifluorene, 699 mg (0.625 mM) of Pd (PPh3)4 3.34 g (24.2 mM) was dissolved in toluene / ethanol / water 100/20/20 mL and refluxed for 24 hours. After completion of the reaction, distillation at room temperature The organic layer was dried over MgSO4 and the solvent was removed by rotary evaporator. The reactants The residue was purified by chromatography (DCM: Hex = 1: 3) and recrystallized from methanol to obtain 6.8 g (89%) of the target compound 8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With bis(tri-tert-butylphosphine)palladium(0); sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; for 6h;Inert atmosphere; Reflux; | o a 500 ml round-bottomed flask under nitrogen was added compound F (10.0 g, 25.25 mmol),9,9-dimethyl-9H-fluoren-2-amine (2.38 g, 11.36 mmol) was completely dissolved in xylene (250 ml), sodium tert-butoxide (1.33 g, 13.89 mol) was added,Bis (tri-tert-butylphosphine) palladium (0) (0.13 g, 0.25 mmol) was added thereto, followed by heating and stirring for 6 hours.After the temperature was lowered to room temperature and the salts were removed by filtration, the xylene was concentrated under reduced pressure and recrystallized from 380 ml of tetrahydrofuran to obtain Compound 15 (16.78 g, yield: 79%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | 4-bromo-9,9'-spirobifluorene(10.0 g, 25.3 mmol)Was dissolved in THF (150 mL), cooled to -78 deg. C, and a normal butyl lithium solution (15 mL, 38 mmol) having a concentration of 2.5 M was poured. Triisopropylborane (9.5 g, 50.6 mmol)And the mixture is stirred for 5 hours.After completion of the reaction, the mixture is quenched with 1N HCl and extracted with ethyl acetate and water. The organic layer was distilled under reduced pressure and purified by column chromatography (EtOAc: Hexane) to synthesize Compound K (8.2 g, 90). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.2% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In toluene; at 105℃; for 24h;Inert atmosphere; | In a 250 ml three-necked flask, under the protection of nitrogen, O.Olmol of 4-bromo-9,9'-spirobifluorene, 0.012 mol of intermediate Jl, and 150 ml of toluene were stirred and mixed, followed by 0.02 mol of sodium carbonate, 1 X l. (T4mol Pd (PPh3) 4, heated to 105 C, refluxing reaction for 24 hours, sampling point plate, shows no bromine residue, the reaction is complete; naturally cooled to room temperature, filtered, the filtrate was evaporated under reduced pressure (-0.09MPa, 85 C), over neutral silica gel column to give the target product, HPLC purity 99.4%, yield 71.2% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76.3% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 105℃; for 24h;Inert atmosphere; | In a 250ml three-neck flask, under nitrogen through added 0.01mol4- bromo-9,9'-spirobifluorene, 0.012 mol ofintermediate F1,150ml stirred mixture of toluene, 0.03 mol of sodium tert-butoxide was then added, 5 × 10-5molPd2(dba)3,5×10-5mol oftri-tert-butylphosphine, heated to 105C, refluxed for 24 hours, sampled on the spot plate, showed no bromine remaining, the reaction was complete; naturallycooled to room temperature, Filtration, the filtrate was evaporated under reduced pressure (-0.09MPa, 85 C), over neutral silica gel column to give the target product,HPLC purity 99.3%, yield 76.3%; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70.7% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In toluene; at 105℃; for 24h;Inert atmosphere; | In a 250 ml three-neck flask, under the protection of nitrogen, add 0.01 mol of 4-bromo-9,9'-spirobifluorene, 0.012 molIntermediate R1, 150 ml of toluene was stirred and mixed, then 0.02 mol of sodium carbonate, 1 x 10-4 mol of Pd(PPh3)4, heated to 105 was added C, reflux reaction for 24 hours, sample point plate showing no bromine remaining, complete reaction; naturally cooled to room temperature, filtered, filtrate Vacuum rotary evaporation (-0.09 MPa, 85C) was performed on a neutral silica gel column to obtain the desired product, HPLC purity 99.2%, yield70.7%; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; for 48h;Reflux; | 2-(9-phenyl-9H-carbazol-3-yl)-5H-benzofuro[3,2- c]carbazole (7 g, 14 mmol), 4-bromo-9,9?-spirobi[fluorene] (6.7 g, 17 mmol), Pd2(dba)3 (0.64 g, 0.7 mmol), tefltributylphosphine (0.17 g, 0.84 mmol) and tert-sodiumbutoxide (3.56 g, 37 mmol) were dissolved in toluene (280 mE). The mixture was refluxed and stirred for 48 hours, and the resultant was extracted 3 times by methylenechloride. The resultant was concentrated under the reduced pressure, washed and colunmed in the silica-gel such that the compound PPH1 was obtained. (2.5 g, yield: 22%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73.7% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 105℃; for 24h;Inert atmosphere; | In a 250 ml three-necked flask, 0.01 mol of 4-bromo-9,9'-spirobifluorene, 0.012 mol of intermediate O1, 150 ml of toluene were added under a nitrogen atmosphere, stirred and mixed uniformly, and then 0.03 mol of sodium t-butoxide was added. ×10-5 mol Pd2 (dba) 3,5×10-5 mol of tri-tert-butylphosphine, heated to 105 C, and refluxed for 24 hours.The sampling point plate shows that there is no bromine residue remaining, the reaction is complete; it is naturally cooled to room temperature, filtered, and the filtrate is subjected to vacuum distillation (-0.09 MPa, 85 C), and passed through a neutral silica gel column to obtain the target product.HPLC purity 99.2%, yield 73.7%; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran;Inert atmosphere; | d) 2-bromobiphenyl (7.88 g, 34.0 mmol) was dissolved in 120 ml of tetrahydrofuran.A solution of n-butyllithium in hexane (2.5 M, 15.6 ml) was added dropwise at -78 C.The joining time is controlled within 10 minutes.Keep this temperature and stir for 1 hour.The obtained intermediate D-1 (8.06 g, 26.0 mmol) was obtained under an argon atmosphere.a solution of tetrahydrofuran (150 ml) was added to the system.Neutralize with aqueous sodium bicarbonate at room temperature,Extracted with dichloromethane,The organic layer was dried over anhydrous magnesium sulfate.Vacuum distillation,The crude product obtained was dissolved in acetic acid (250 ml).Aqueous hydrochloric acid (25 ml, 35 wt%) was added.Reflux for 12 hours,Cool to room temperature,Purified by column chromatography (dichloromethane/n-hexane).Bromide B-1 was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73.9% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; for 12h;Inert atmosphere; Reflux; | In 250 ml Schlenk bottle, add 4 - bromo - 9, 9' - [...] 10.19 g (25.77 mmol), aniline 3.00 g (15.00 mmol), palladium acetate 0.36 g (1.6 mmol), tri-[...] four fluoroborates 0.93 g (3.22 mmol), sodium tert-9.29 g (96.64 mmol), toluene 150 ml, under protection of argon, reflux stirring reaction for 12 hours, reaction finishes. Evaporating the solvent, for 100 ml methylene chloride and 50 ml of water to dissolve the residue, water washing, separating the organic layer, the aqueous layer for 30 ml dichloromethane extraction twice, combined with the organic layer, after evaporating the solvent, the residue by column chromatography (silica gel as a 350 mesh, showering liquid is petroleum ether: dichloromethane=3:1 (V/V)), evaporating the solvent, after drying, to obtain 9.70 g white solid, the yield of 73.9%. |
With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; at 80℃; for 8h;Inert atmosphere; | Preparation of intermediate M-1: bromide B-1 (5.93 g, 15 mmol), aromatic amine compound A-1 (1.40 g, 15 mmol), sodium tert-butoxide (2.88 g, 30 mmol) were added under argon atmosphere. In 150 ml of dehydrated toluene, palladium acetate (0.07 g, 0.3 mmol) and tri-tert-butylphosphine (0.06 g, 0.3 mmol) were added under stirring, and the mixture was reacted at 80 C for 8 hours. After cooling, it was filtered through a celite/silica gel funnel.The filtrate was subjected to distillation under reduced pressure to remove an organic solvent, and the obtained residue was recrystallized from toluene.The resulting solid was collected by filtration and dried to give Intermediate M-1. | |
With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; at 80℃; for 8h;Inert atmosphere; | bromide B-1 (5.93 g, 15 mmol), aromatic amine compound A-1 (1.40 g, 15 mmol), sodium tert-butoxide (2.88 g, 30 mmol) were added under argon atmosphere. In 150 ml of dehydrated toluene, palladium acetate (0.07 g, 0.3 mmol) and tri-tert-butylphosphine (0.06 g, 0.3 mmol) were added under stirring, and the mixture was reacted at 80 C for 8 hours. After cooling, it was filtered through a celite/silica gel funnel, and the organic solvent was removed by distillation under reduced pressure. The obtained residue was recrystallized from toluene, and the obtained solid was filtered and dried to give Intermediate M-1 |
With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; potassium tert-butylate; In toluene; at 105℃; for 24h;Inert atmosphere; | 250 ml three-necked bottle, 0.1 mol of raw material F1, 0.12 mol of raw material G1,0.3 mol of potassium t-butoxide, 1 × 10-3mol of Pd2(dba)3, 1 × 10-3mol wereadded under a nitrogen atmosphere.P(t-Bu)3, 150ml toluene, heated to 105 C for24 hours, sampling the plate, the reaction is complete; naturally cooled, filtered, the filtrate is steamed, passed through a silica gel column to obtain the intermediate H1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
a) Methyl 2-iodo-3-bromobenzoate (10.0 g, 30 mmol), phenylboronic acid (3·66 g, 30 mmol) and tetrakis(triphenylphosphine)palladium (1.7 g, 1.46 mmol) under nitrogen atmosphere Dissolved in 100 ml of tetrahydrofuran, stirred for 30 minutes, then added dropwise 50 ml of potassium carbonate aqueous solution (1.63 g, 11.18mm0l) over 20 minutes, refluxed overnight, washed with water, extracted with dichloromethane, and evaporated to remove organic solvent; b) The obtained solid (8.5 g, 255. Ommol) and sodium hydroxide (1.2 g, 30 mmol) were dissolved in 100 ml of ethanol, refluxed for 6 hours, cooled to room temperature, neutralized with 2M hydrochloric acid, and filtered. Recrystallization from ethanol; c) The obtained crystals (10 g, 30 mmol) were dissolved in 300 ml of methanesulfonic acid, stirred at 30 C for 24 hours, poured into ice water, filtered, washed with water, dried, and stirred with aqueous sodium hydrogencarbonate for 3 hr, filtered, washed with water Recrystallization from ethanol to give intermediate D-1; d) 2-bromobiphenyl (7.88 g, 34.0 mmol) was dissolved in 120 ml of tetrahydrofuran, and n-butyllithium in hexane was added dropwise at -78 C. Solution (2.5 M, 15.6 ml), the addition time was controlled within 10 minutes, the temperature was kept at this temperature for 1 hour, and the obtained intermediate D-1 (8.06 g, 26.0 mmol) in tetrahydrofuran (150 ml) was added to the system under argon atmosphere. The mixture was neutralized with an aqueous solution of sodium hydrogencarbonate at room temperature, and extracted with methylene chloride. The organic layer was dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The crude product was dissolved in acetic acid (250 ml), and aqueous hydrochloric acid (25 ml, 35 wt%) The mixture was refluxed for 12 hours, cooled to room temperature, and purified by column chromatography (dichloromethane/hexane) to give bromide B-1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In toluene; for 16h;Reflux; | The obtained bromide B-1 (7.89 g, 20 mmol), pinacol borate (6.22 g, 24 mmol), 1,1'-bis(diphenylphosphino)-ferrocene-palladium dichloride (II) Dichloromethane complex (0.49 g, 0.6 mmol), potassium acetate (5.90 g, 60 mmol) and 79 ml of toluene were reacted under reflux for 16 hours, cooled, added with 26 ml of water, stirred for 30 minutes, and the organic phase was separated and passed. The celite bed was filtered, and then the organic solvent was evaporated, and the obtained crude product was recrystallized from heptane/toluene. The obtained solid (6.64 g, 15 mmol), p-bromoiodobenzene (4.05 g, 14.3 mmol), Tetrakis(triphenylphosphine)palladium (0.35 g, 0.3 mmol), toluene (43 ml), sodium carbonate aqueous solution (2M, 21 ml) was added to the flask, refluxed for 8 hours, cooled to room temperature, extracted with toluene, and the organic phase was saturated. After washing with brine, the organic phase was dried and purified by column chromatography to give bromide B-42 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In 1,4-dioxane; at 110℃; for 1h; | In a one-neck round bottom flask, a 1,4-dioxane (700 ml) mixture of 3-bromospirobifluorene (40 g, 101.2 mmol), <strong>[190788-59-1]4,4,5,5-tetramethyl-2-(2-nitrophenyl)-1,3,2-dioxaborolane</strong> (25.2 g, 101.2 mmol), Pd(PPh3)4 (11.6 g, 10.12 mmol), and CsF (30.7 g, 202.4 mmol) was refluxed at 110 for 1 hour. The mixture was extracted with methylene chloride (MC), and then the organic layer was dried over MgSO4. The organic layer was concentrated, and then separated with column chromatography (SiO2, Hexane:MC=3:1) to obtain Compound 2-1 (30 g, 67%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; for 12h;Inert atmosphere; Reflux; | The compound 4-bromo-9.9-spirobifluorene (11.94g, 30mmol) and 3,9-bicarbazole (9.99g, 30mmol) were added to a three-necked flask, stirred and dissolved with 300 mL of toluene, protected with nitrogen, and then added. Pd (dba) 2 862.5 mg, 1.5 mmol) and sodium tert-butoxide (5.76 g, 60 mmol), followed by 10 mL of a 10% solution of tri-tert-butylphosphine in toluene. The reaction solution was stirred and refluxed for 12 hours, cooled, and the reaction mixture was washed three times with 100 ml of water.Dry over anhydrous sodium sulfate and then remove the solvent by evaporation.The residue was purified by hydrazine/PE (1:10) through a column.The white solid was obtained as Compound 4 (9.30 g, yield 48%). |
Tags: 1161009-88-6 synthesis path| 1161009-88-6 SDS| 1161009-88-6 COA| 1161009-88-6 purity| 1161009-88-6 application| 1161009-88-6 NMR| 1161009-88-6 COA| 1161009-88-6 structure
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Code | Phrase |
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H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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