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Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 1 h; Inert atmosphere Stage #2: for 1 h; Inert atmosphere
2,7-dibromo-9,9-dimethylfluorene (14.8 g, 42.4 mmol)Add to three bottles,100 mL of THF was added,Nitrogen protection,-78 deg.] C for 30 minutes,Then, 21 mL of n-butyllithium (2.5 M)Reaction for 1 hour, againAdd triisopropyl borate 14g,Low temperature reaction for 1 hour,Gradually restored room temperature.After the addition of 2M hydrochloric acid to the solution, the pH value of the solution was 4-5, and the aqueous layer was extracted with ethyl acetate. The organic layer was combined and dried to give intermediate A1 (9.5 g, yield 80percent ).
70%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -70 - -65℃; for 6 h; Inert atmosphere Stage #2: at -70 - 20℃; Stage #3: With hydrogenchloride In tetrahydrofuran; hexane; water
(4-2) Synthesis of Intermediate 8; Into a 3 liter three-necked flask, 35 g (0.1 mole) of Intermediate 7 and 1 liter of THF were placed under the stream of argon, and the obtained solution was cooled at -65° C. To the cooled solution, 220 ml of a solution of n-butyllithium (0.22 moles, a 1 mole/liter hexane solution) was slowly added. After the reaction fluid was stirred at -70° C. for 6 hours, 45 g (0.24 moles) of boronic acid triisopropoxide was slowly added at -65° C. The resultant fluid was stirred at -70° C. for 1 hour and then at the room temperature for one night. After the reaction was completed, dilute hydrochloric acid was added to the reaction fluid to adjust pH at 3, and the organic layer was separated, washed with a saturated aqueous solution of sodium chloride and dried with magnesium sulfate. The solvent was removed by distillation using a rotary evaporator, and ethyl acetate was added to the residue. The obtained crystals were separated by filtration and washed with hexane three times, and 20 g of Intermediate 8 of the object compound was obtained (white crystals; the yield: 70percent).
Reference：
[1] Patent: CN106699780, 2017, A, . Location in patent: Paragraph 0047; 0048; 0049; 0050
[2] Patent: US8058450, 2011, B2, . Location in patent: Page/Page column 43-44
[3] Luminescence, 2015, vol. 30, # 5, p. 549 - 555
2
[ 28320-32-3 ]
[ 866100-14-3 ]
Yield
Reaction Conditions
Operation in experiment
70%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -70 - -65℃; for 6 h; Stage #2: With Triisopropyl borate In tetrahydrofuran; hexane at -70 - 20℃; Stage #3: With hydrogenchloride; water In tetrahydrofuran; hexane
In a stream of argon, 35 g (0.1 mol) of Intermediate 6 and 1 L of tetrahydrofuran (THF) were added to a 3-L three-necked flask, and the whole was cooled to - 65°C. Subsequently, 220 mL (0.22 mol, 1 mol/L (hexane)) of n-butyllithiumwere slowlyaddedto the resultant. After the reaction liquid had been stirred at - 70°C for 6 hours, 45 g (0.24 mol) of boronic triisopropoxide were slowly added to the reaction liquid at - 65°C, and the whole was stirred at - 70°C for 1 hour. After that, the resultant was stirred at room temperature overnight. After the completion of the reaction, dilute hydrochloric acid was added to the reaction liquid to adjust the pH of the liquid to 3, and an organic layer was separated and washed with a saturated salt solution. After the washed product had been dried with magnesium sulfate, the solvent was removed by distillation with a rotary evaporator, and ethyl acetate was added to the remainder. The resultant crystal was separated by filtration, and was washed with hexane three times, whereby 20 g of Intermediate 7 (white crystal, 70percent yield) as a target were obtained.
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 1 h; Inert atmosphere Stage #2: for 1 h; Inert atmosphere Stage #3: Inert atmosphere
Dibromo-9,9-dimethylfluorene (14.9 g, 42.4 mmol) was added to a three-necked flask and 100 mL of THF was added thereto and protected by nitrogen. The mixture was stirred at -78 ° C for 30 minutes and then n-butyllithium M) 21 mL, reacted for 1 hour, added triisopropyl borate 14 g, reacted at low temperature for 1 hour, and gradually returned to room temperature.In the post-treatment process, 2M hydrochloric acid was added to the system to make the solution have a pH of 4-5, and the mixture was allowed to stand for liquid separation. The aqueous layer was extracted with ethyl acetate, and the organic layers were combined and spin-dry.2,7-Diboronic acid-9,9-dimethylhydrazine (8.9 g, 75percent yield) was obtained.
Reference：
[1] Patent: CN107698487, 2018, A, . Location in patent: Paragraph 0093-0095
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 8h;Heating / reflux;
In a stream of argon, 14 g (0.05 mol) of Intermediate 7, 25 g (0.11 mol) of 2-bromobenzoate ethylester, 2.8 g (5 mmol) of tetrakistriphenylphosphinepalladium(0), 200 mL of toluene, and the mixture of 16 g (0.15 mol) of sodium carbonate and 150 mL of water were added to a 1-L three-necked flask, and the whole was refluxed under heat for 8 hours. After the completion of the reaction, an organic layer was washed with water and dried with magnesium sulfate, and then the solvent was removed by distillation with a rotary evaporator. The resultant coarse crystal was recrystallized with ethanol, whereby 12 g of Intermediate 8 (white crystal, 50% yield) as a target were obtained.
50%
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 8h;Reflux; Inert atmosphere;
(4-3) Synthesis of Intermediate 9; Into a 1 liter three-necked flask, 14 g (0.05 moles) of Intermediate 8, 25 g (0.11 moles) of ethyl 2-bromobenzoate, 2.8 g (5 mmole) of tetrakistriphenylphosphinepalladium(0), 200 ml of toluene and a solution prepared by dissolving 16 g (0.15 moles) of sodium carbonate into 150 ml of water were placed under the stream of argon, and the resultant mixture was heated under the refluxing condition for 8 hours. After the reaction was completed, the organic layer was washed with water and dried with magnesium sulfate, and the solvent was removed by distillation using a rotary evaporator. The obtained crude crystals were recrystallized from ethanol, and 12 g of Intermediate 9 of the object compound was obtained (white crystals; the yield: 50%).
In a stream of argon, 35 g (0.1 mol) of Intermediate 6 and 1 L of tetrahydrofuran (THF) were added to a 3-L three-necked flask, and the whole was cooled to - 65C. Subsequently, 220 mL (0.22 mol, 1 mol/L (hexane)) of n-butyllithiumwere slowlyaddedto the resultant. After the reaction liquid had been stirred at - 70C for 6 hours, 45 g (0.24 mol) of boronic triisopropoxide were slowly added to the reaction liquid at - 65C, and the whole was stirred at - 70C for 1 hour. After that, the resultant was stirred at room temperature overnight. After the completion of the reaction, dilute hydrochloric acid was added to the reaction liquid to adjust the pH of the liquid to 3, and an organic layer was separated and washed with a saturated salt solution. After the washed product had been dried with magnesium sulfate, the solvent was removed by distillation with a rotary evaporator, and ethyl acetate was added to the remainder. The resultant crystal was separated by filtration, and was washed with hexane three times, whereby 20 g of Intermediate 7 (white crystal, 70% yield) as a target were obtained.
2,7-dibromo-9,9-dimethylfluorene (14.8 g, 42.4 mmol)Add to three bottles,100 mL of THF was added,Nitrogen protection,-78 deg.] C for 30 minutes,Then, 21 mL of n-butyllithium (2.5 M)Reaction for 1 hour, againAdd triisopropyl borate 14g,Low temperature reaction for 1 hour,Gradually restored room temperature.After the addition of 2M hydrochloric acid to the solution, the pH value of the solution was 4-5, and the aqueous layer was extracted with ethyl acetate. The organic layer was combined and dried to give intermediate A1 (9.5 g, yield 80% ).
70%
(4-2) Synthesis of Intermediate 8; Into a 3 liter three-necked flask, 35 g (0.1 mole) of Intermediate 7 and 1 liter of THF were placed under the stream of argon, and the obtained solution was cooled at -65 C. To the cooled solution, 220 ml of a solution of n-butyllithium (0.22 moles, a 1 mole/liter hexane solution) was slowly added. After the reaction fluid was stirred at -70 C. for 6 hours, 45 g (0.24 moles) of boronic acid triisopropoxide was slowly added at -65 C. The resultant fluid was stirred at -70 C. for 1 hour and then at the room temperature for one night. After the reaction was completed, dilute hydrochloric acid was added to the reaction fluid to adjust pH at 3, and the organic layer was separated, washed with a saturated aqueous solution of sodium chloride and dried with magnesium sulfate. The solvent was removed by distillation using a rotary evaporator, and ethyl acetate was added to the residue. The obtained crystals were separated by filtration and washed with hexane three times, and 20 g of Intermediate 8 of the object compound was obtained (white crystals; the yield: 70%).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; for 10h;Reflux;
A solution of tetraphenylphenylphosphine palladium (2.1 g, 1.83 mmol)And potassium carbonate (75.7 g, 549 mmol)Was added to a solution of intermediate Al (51.6 g, 183 mmol)And intermediate C1 (111.4 g, 384 mmol)In a degassed tetrahydrofuran (500 mL)And the mixture was heated under reflux for 10 hours.The reaction mixture was cooled to room temperature, after which the solvent was removed.The target product TM1 was obtained by silica gel column chromatography(49.5 g, 65% theoretical).
Dibromo-9,9-dimethylfluorene (14.9 g, 42.4 mmol) was added to a three-necked flask and 100 mL of THF was added thereto and protected by nitrogen. The mixture was stirred at -78 C for 30 minutes and then n-butyllithium M) 21 mL, reacted for 1 hour, added triisopropyl borate 14 g, reacted at low temperature for 1 hour, and gradually returned to room temperature.In the post-treatment process, 2M hydrochloric acid was added to the system to make the solution have a pH of 4-5, and the mixture was allowed to stand for liquid separation. The aqueous layer was extracted with ethyl acetate, and the organic layers were combined and spin-dry.2,7-Diboronic acid-9,9-dimethylhydrazine (8.9 g, 75% yield) was obtained.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; for 4h;Reflux;
Tetrakistriphenylphosphine palladium (2.1 g, 1.83 mmol)And potassium carbonate (75.7g, 549mmol) was added to 9,9-dimethyl-fluorene-2,7-diboronic acid (51.4g, 183mmol)And a solution of compound c3 (174.7 g, 384 mmol) in degassed tetrahydrofuran (500 mL)And the mixture was heated under reflux for 4 hours.Hot and suction filtration,Get a lot of solids,Dissolve the solid with a solvent,After concentration,The compound 50 (120.6 g, yield 70%) was obtained by silica gel column chromatography.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 100℃; for 24h;
1-1 Example 1-1) Preparation of Intermediate 1
9,9-dimethylfluorene-2,7-diboronic acid (13 g, 46 mmol), 1-bromo-4-chloro-2-nitrobenzene (26 g, 11 mmol) in a 500 mL round-bottom flask under nitrogen atmosphere ), tetrakis(triphenylphosphine)palladium (2.7 g, 2.3 mmol), potassium carbonate (19.1 g, 138 mmol) were added, and 1,4-dioxane 300 mL and water 60 mL were added. The temperature of the reactor was raised to 100 oC and stirred for 24 hours. When the reaction is complete, the temperature is lowered to room temperature, water is added to precipitate a solid, and the solid is filtered. Ethanol is added to the filtered solid and stirred to dissolve only impurities and filter. The solid insoluble in ethanol was dissolved in tetrahydrofuran and then crystallized with ethanol to obtain Intermediate 1 (20.2 g, yield 80%).
General Procedures for the Preparation of 1,1'-biphenyl-4-d (2a) :
General procedure: To a stirring solution of biphenylboronic acid (59.4 mg, 0.3 mmol) in [bmim]PF6 (0.2 mL) was added D2O (120 mg, 6 mmol) at room temperature. The solution was warmed to 70 °C and stirred for 6 h. The reaction was monitored by TLC. After completed, the reaction was purified by a flash column chromatography on silica gel using petroleum ether as eluent to obtain the product as white solid (42.8 mg, 92% yield).
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