2-Bromo-9-fluorenone

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A catalyst solution was prepared by mixing tris(dibenzylideneacetone)dipalladium (Pd2(dba)3; 20 mg, 0.022 mmol; Alfa) and racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP; 38 mg, 0.061 mmol; Strem) in toluene (1 mL) and heating the mixture to 90° C. for 15 min. The solution was cooled, and then added to a mixture of 1,4-diazabicyclo[3.2.2]nonane (112 mg, 0.889 mmol; see J. Med. Chem. 1993, 36, 2311) and 2-bromofluoren-9-one (320 mg, 1.24 mmol; Aldrich) in toluene (3 mL). Sodium tert-butoxide (120 mg, 1.25 mmol; Aldrich) was then added, and the reaction mixture was flushed with nitrogen and heated to 80-85° C. overnight. After cooling to room temperature, the mixture was filtered through diatomaceous earth and purified by chromatography (35 g silica gel, 1-16% gradient of NH4OH-MeOH (1:10) in CH2Cl2) to afford the title compound (116 mg, 0.382 mmol; 43% yield): 1H NMR (300 MHz, CD3OD) δ ppm 7.48 (d, J=7 Hz, 1H), 7.39-7.44 (m, 3H), 7.14 (ddd, J=7, 6, 3 Hz, 1H), 7.09 (d, J=3 Hz, 1H), 6.93 (dd, J=8, 3 Hz, 1H), 4.10-4.17 (m, 1H), 3.66 (dd, J=6, 5 Hz, 2H), 2.95-3.17 (m, 6H), 2.09-2.23 (m, 2H), 1.84 (ddd, J=19, 10, 5 Hz, 2H); MS (DCl/NH3): m/z 305 (M+1)+. A catalyst solution was prepared The solution was cooled the reaction mixture was flushed with nitrogen heated to 80-85° C. overnight After cooling to room temperature the mixture was filtered through diatomaceous earth purified by chromatography (35 g silica gel, 1-16% gradient of NH4OH-MeOH (1:10) in CH2Cl2)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A catalyst solution was prepared by mixing tris(dibenzylideneacetone)dipalladium (Pd2(dba)3; 20 mg, 0.022 mmol; Alfa) and racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP; 38 mg, 0.061 mmol; Strem) in toluene (1 mL) and heating the mixture to 90° C. for 15 min. The solution was cooled, and then added to a mixture of 1,4-diazabicyclo[3.2.2]nonane (112 mg, 0.889 mmol; see J. Med. Chem. 1993, 36, 2311) and 2-bromofluoren-9-one (320 mg, 1.24 mmol; Aldrich) in toluene (3 mL). Sodium tert-butoxide (120 mg, 1.25 mmol; Aldrich) was then added, and the reaction mixture was flushed with nitrogen and heated to 80-85° C. overnight. After cooling to room temperature, the mixture was filtered through diatomaceous earth and purified by chromatography (35 g silica gel, 1-16% gradient of NH4OH-MeOH (1:10) in CH2Cl2) to afford the title compound (116 mg, 0.382 mmol; 43% yield): 1H NMR (300 MHz, CD3OD) δ ppm 7.48 (d, J=7 Hz, 1H), 7.39-7.44 (m, 3H), 7.14 (ddd, J=7, 6, 3 Hz, 1H), 7.09 (d, J=3 Hz, 1H), 6.93 (dd, J=8, 3 Hz, 1H), 4.10-4.17 (m, 1H), 3.66 (dd, J=6, 5 Hz, 2H), 2.95-3.17 (m, 6H), 2.09-2.23 (m, 2H), 1.84 (ddd, J=19, 10, 5 Hz, 2H); MS (DCl/NH3): m/z 305 (M+1)+. A catalyst solution was prepared The solution was cooled the reaction mixture was flushed with nitrogen heated to 80-85° C. overnight After cooling to room temperature the mixture was filtered through diatomaceous earth purified by chromatography (35 g silica gel, 1-16% gradient of NH4OH-MeOH (1:10) in CH2Cl2)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.26 g (0.052 mol) of magnesium was put in a 100 mL three-necked flask to which a dropping funnel and a Dimroth condenser were connected, and the flask was evacuated. The magnesium was activated by 30 minutes of heating and stirring. After cooling to room temperature, the flask was placed under a nitrogen gas flow. 5 mL of diethyl ether and several drops of dibromoethane were added, and 11.65 g (0.050 mol) of 2-bromobiphenyl dissolved in 15 mL of diethyl ether was slowly delivered from the dropping funnel by drops into the mixture. After the dropping was complete, the mixture was refluxed for 3 hours and made into a Grignard reagent. 11.7 g (0.045 mol) of 2-bromo-9-fluorenone and 40 mL of diethyl ether were put in a 200 mL three-necked flask to which a dropping funnel and a Dimroth condenser were connected. To this reaction solution, the synthesized Grignard reagent was slowly delivered by drops from the dropping funnel. After the dropping was complete, the mixture was refluxed for 2 hours, and then stirred at room temperature for about 12 hours. After the reaction was complete, the solution was washed twice with saturated ammonia chloride solution. An aqueous layer was extracted twice with ethyl acetate and combined with an organic layer, and the solution was washed with a saturated saline solution. After drying with magnesium sulfate, suction filtration and concentration were conducted, and a solid of 9-(biphenyl-2-yl)-2-bromo-9-fluorenol was obtained, weighing 18.76 g in a yield of 90%. the flask was evacuated of heating 5 mL of diethyl ether and several drops of dibromoethane were added the mixture was refluxed for 3 hours the mixture was refluxed for 2 hours stirred at room temperature for about 12 hours the solution was washed twice with saturated ammonia chloride solution An aqueous layer was extracted twice with ethyl acetate the solution was washed with a saturated saline solution After drying with magnesium sulfate, suction filtration and concentration

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A catalyst solution was prepared by mixing tris(dibenzylideneacetone)dipalladium (Pd2(dba)3; 20 mg, 0.022 mmol; Alfa) and racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP; 38 mg, 0.061 mmol; Strem) in toluene (1 mL) and heating the mixture to 90° C. for 15 min. The solution was cooled, and then added to a mixture of 1,4-diazabicyclo[3.2.2]nonane (112 mg, 0.889 mmol; see J. Med. Chem. 1993, 36, 2311) and 2-bromofluoren-9-one (320 mg, 1.24 mmol; Aldrich) in toluene (3 mL). Sodium tert-butoxide (120 mg, 1.25 mmol; Aldrich) was then added, and the reaction mixture was flushed with nitrogen and heated to 80-85° C. overnight. After cooling to room temperature, the mixture was filtered through diatomaceous earth and purified by chromatography (35 g silica gel, 1-16% gradient of NH4OH-MeOH (1:10) in CH2Cl2) to afford the title compound (116 mg, 0.382 mmol; 43% yield): 1H NMR (300 MHz, CD3OD) δ ppm 7.48 (d, J=7 Hz, 1H), 7.39-7.44 (m, 3H), 7.14 (ddd, J=7, 6, 3 Hz, 1H), 7.09 (d, J=3 Hz, 1H), 6.93 (dd, J=8, 3 Hz, 1H), 4.10-4.17 (m, 1H), 3.66 (dd, J=6, 5 Hz, 2H), 2.95-3.17 (m, 6H), 2.09-2.23 (m, 2H), 1.84 (ddd, J=19, 10, 5 Hz, 2H); MS (DCI/NH3): m/z 305 (M+1)+. A catalyst solution was prepared The solution was cooled the reaction mixture was flushed with nitrogen heated to 80-85° C. overnight After cooling to room temperature the mixture was filtered through diatomaceous earth purified by chromatography (35 g silica gel, 1-16% gradient of NH4OH-MeOH (1:10) in CH2Cl2)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.26 g (0.052 mol) of magnesium was put in a 100 mL three-necked flask to which a dropping funnel and a Dimroth condenser were connected, and the flask was evacuated. The magnesium was activated by 30 minutes of heating and stirring. After cooling to room temperature, the flask was placed under a nitrogen gas flow. 5 mL of diethyl ether and several drops of dibromoethane were added, and 11.65 g (0.050 mol) of 2-bromobiphenyl dissolved in 15 mL of diethyl ether was slowly delivered from the dropping funnel by drops into the mixture. After the dropping was complete, the mixture was refluxed for 3 hours and made into a Grignard reagent. 11.7 g (0.045 mol) of 2-bromo-9-fluorenone and 40 mL of diethyl ether were put in a 200 mL three-necked flask to which a dropping funnel and a Dimroth condenser were connected. To this reaction solution, the synthesized Grignard reagent was slowly delivered by drops from the dropping funnel. After the dropping was complete, the mixture was refluxed for 2 hours, and then stirred at room temperature for about 12 hours. After the reaction was complete, the solution was washed twice with saturated ammonia chloride solution. An aqueous layer was extracted twice with ethyl acetate and combined with an organic layer, and the solution was washed with a saturated saline solution. After drying with magnesium sulfate, suction filtration and concentration were conducted, and a solid of 9-(biphenyl-2-yl)-2-bromo-9-fluorenol was obtained, weighing 18.76 g in a yield of 90%. the flask was evacuated of heating 5 mL of diethyl ether and several drops of dibromoethane were added the mixture was refluxed for 3 hours the mixture was refluxed for 2 hours stirred at room temperature for about 12 hours the solution was washed twice with saturated ammonia chloride solution An aqueous layer was extracted twice with ethyl acetate the solution was washed with a saturated saline solution After drying with magnesium sulfate, suction filtration and concentration

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.26 g (0.052 mol) of magnesium was put in a 100 mL three-necked flask to which a dropping funnel and a Dimroth condenser were connected, and the flask was evacuated. The magnesium was activated by 30 minutes of heating and stirring. After cooling to room temperature, the flask was placed under a nitrogen gas flow. 5 mL of diethyl ether and several drops of dibromoethane were added, and 11.65 g (0.050 mol) of 2-bromobiphenyl dissolved in 15 mL of diethyl ether was slowly delivered from the dropping funnel by drops into the mixture. After the dropping was complete, the mixture was refluxed for 3 hours and made into a Grignard reagent. 11.7 g (0.045 mol) of 2-bromo-9-fluorenone and 40 mL of diethyl ether were put in a 200 mL three-necked flask to which a dropping funnel and a Dimroth condenser were connected. To this reaction solution, the synthesized Grignard reagent was slowly delivered by drops from the dropping funnel. After the dropping was complete, the mixture was refluxed for 2 hours, and then stirred at room temperature for about 12 hours. After the reaction was complete, the solution was washed twice with saturated ammonia chloride solution. An aqueous layer was extracted twice with ethyl acetate and combined with an organic layer, and the solution was washed with a saturated saline solution. After drying with magnesium sulfate, suction filtration and concentration were conducted, and a solid of 9-(biphenyl-2-yl)-2-bromo-9-fluorenol was obtained, weighing 18.76 g in a yield of 90%. the flask was evacuated of heating 5 mL of diethyl ether and several drops of dibromoethane were added the mixture was refluxed for 3 hours the mixture was refluxed for 2 hours stirred at room temperature for about 12 hours the solution was washed twice with saturated ammonia chloride solution An aqueous layer was extracted twice with ethyl acetate the solution was washed with a saturated saline solution After drying with magnesium sulfate, suction filtration and concentration

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.26 g (0.052 mol) of magnesium was put in a 100 mL three-necked flask to which a dropping funnel and a Dimroth condenser were connected, and the flask was evacuated. The magnesium was activated by 30 minutes of heating and stirring. After cooling to room temperature, the flask was placed under a nitrogen gas flow. 5 mL of diethyl ether and several drops of dibromoethane were added, and 11.65 g (0.050 mol) of 2-bromobiphenyl dissolved in 15 mL of diethyl ether was slowly delivered from the dropping funnel by drops into the mixture. After the dropping was complete, the mixture was refluxed for 3 hours and made into a Grignard reagent. 11.7 g (0.045 mol) of 2-bromo-9-fluorenone and 40 mL of diethyl ether were put in a 200 mL three-necked flask to which a dropping funnel and a Dimroth condenser were connected. To this reaction solution, the synthesized Grignard reagent was slowly delivered by drops from the dropping funnel. After the dropping was complete, the mixture was refluxed for 2 hours, and then stirred at room temperature for about 12 hours. After the reaction was complete, the solution was washed twice with saturated ammonia chloride solution. An aqueous layer was extracted twice with ethyl acetate and combined with an organic layer, and the solution was washed with a saturated saline solution. After drying with magnesium sulfate, suction filtration and concentration were conducted, and a solid of 9-(biphenyl-2-yl)-2-bromo-9-fluorenol was obtained, weighing 18.76 g in a yield of 90%. the flask was evacuated of heating 5 mL of diethyl ether and several drops of dibromoethane were added the mixture was refluxed for 3 hours the mixture was refluxed for 2 hours stirred at room temperature for about 12 hours the solution was washed twice with saturated ammonia chloride solution An aqueous layer was extracted twice with ethyl acetate the solution was washed with a saturated saline solution After drying with magnesium sulfate, suction filtration and concentration

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.3 g (52 mmol) of magnesium was put into a 200 mL three-neck flask and stirred for 0.5 hours while reducing pressure with a rotary pump. Then, under a nitrogen gas stream, 5.0 mL of diethyl ether and one drop of dibromoethane were added. A solution in which 12 g (50 mmol) of 2-bromophenyl was dissolved in 15 mL of diethyl ether was dropped into this mixture at a pace that maintained reflux flow. After completion of dropping, the reaction mixture was refluxed at 50° C. for 3 hours so as to become a Grignard reagent. 12 g (45 mmol) of 2-bromo-9-fluorenone was put into a 200 mL three-neck flask, and after nitrogen substitution in the flask was carried out, 40 mL of diethyl ether was added into the flask. The synthesized Grignard reagent was dropped into this solution, and after completion of dropping, the solution was refluxed at 50° C. for 3 hours, and then stirred at room temperature for 24 hours. After completion of a reaction, the reaction solution was washed with water, and a water layer was extracted with ethyl acetate. The extracted solution and an organic layer were combined and washed with saturated saline, and then dried with magnesium sulfate. After drying, this mixture was subjected to suction filtration, and when a filtrate was concentrated, 19 g of a light yellow, powdery solid of 9-(biphenyl-2-yl)-2-bromofluoren-9-ol that was a target matter was obtained with the yield of 91%. was dropped into this mixture at a pace that maintained reflux flow the solution was refluxed at 50° C. for 3 hours stirred at room temperature for 24 hours After completion of a reaction the reaction solution was washed with water a water layer was extracted with ethyl acetate washed with saturated saline dried with magnesium sulfate After drying this mixture was subjected to suction filtration, and when a filtrate was concentrated was obtained with the yield of 91%

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9.8 g (40 mmol) of 2-bromofluorene, 40 mL of pyridine, and 1.5 mL of tetrabutylammonium hydroxide (1.0 mol/1 methanol solution) were put into a 200 mL three-neck flask. This solution was stirred under air at room temperature for 24 hours. After completion of a reaction, 40 m/L of glacial acetic acid was added to the reaction solution and stirred for 1 hour. Then, the reaction solution was washed with water and a water layer was extracted with ethyl acetate. The extracted solution and an organic layer were combined and washed with saturated saline, and then dried with magnesium sulfate. After drying, this mixture was subjected to suction filtration, and a filtrate was concentrated. When an obtained solid was recrystallized with ethanol, 7.9 g of a yellow, powdery solid of 2-bromo-9-fluorenone that was a target matter was obtained with the yield of 76%. was added to the reaction solution stirred for 1 hour Then, the reaction solution was washed with water a water layer was extracted with ethyl acetate washed with saturated saline dried with magnesium sulfate After drying this mixture was subjected to suction filtration a filtrate was concentrated When an obtained solid was recrystallized with ethanol, 7.9 g of a yellow, powdery solid of 2-bromo-9-fluorenone that was obtained with the yield of 76%

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromo-9H-fluoren-9-one (100 mg, 0.39 mmol) in EtOH (10 mL) and water (3 mL) was added hydroxylamine hydrochloride (54 mg, 0.77 mmol). The mixture was then heated to reflux for 1 h. The solvent was then removed in vacuo, and to the residue was added aqueous NaHCO3. The solid was then filtered and dried to give the title product. LRMS (M+H)+ 274.2. The mixture was then heated to reflux for 1 h The solvent was then removed in vacuo to the residue was added aqueous NaHCO3 The solid was then filtered dried