2,7-dibromofluoren-9-one

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

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

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

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

Procedure: A solution of TFAA (2.1 mL, 3.15 mmol) in dichloromethane (5 mL) was added dropwise to a suspension of 2,7-dibromo-fluoren-9-one (3.3 g, 10 mmol) and H2O2-urea (1.4 g, 15 mL) in dichloromethane (50 mL). The mixture was stirred at room temperature for 48 hours, a second portion of H2O2-urea was added, and stirring was continued at room temperature for a further 72 hours. The mixture was filtered, the organic phase was extracted with water (50 mL), and dried over Na2SO4. After removal of solvent, the residue was heated with 2N NaOH at 80° C. for 10 minutes, filtered, the cooled filtrate extracted with ether. The aqueous phase was acidified with 2N HCl and extracted with ethyl acetate (200 mL). HCl (2 mL 4M solution) was added to the ethyl acetate and heated for 2 hours. The solvent was removed under vacuum, the residue was recrystallized from ethyl acetate/ethanol to give the final product 3,8-Dibromo-benzo[c]chromen-6-one as a white solid (1.5 g, 40%). stirring was continued at room temperature for a further 72 hours The mixture was filtered the organic phase was extracted with water (50 mL) dried over Na2SO4 After removal of solvent the residue was heated with 2N NaOH at 80° C. for 10 minutes filtered the cooled filtrate extracted with ether extracted with ethyl acetate (200 mL) HCl (2 mL 4M solution) was added to the ethyl acetate heated for 2 hours The solvent was removed under vacuum the residue was recrystallized from ethyl acetate/ethanol

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

Procedure: Followed the procedure used to prepare 4,4,5,5-tetramethyl-2-[7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-9,10-dihydro-phenanthren-2-yl]-[1,3,2]dioxaborolane, except that 2,7-dibromo-9-fluorenone was used instead of 2,7-dibromo-9,10-dihydro-phenanthrene.

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

Procedure: The Grignard reagent prepared from 0.72 g (30 mmol) of magnesium turnings and 5.1 ml (30 mmol) of 2-bromobiphenyl in 15 ml of diethyl ether is added dropwise over a period of 2 hours, while stirring (in an ultrasonic bath), to a boiling suspension of 10.0 g (29.6 mmol) of 2,7-dibromo-9-fluorenone in 100 ml of dry diethyl ether. After the addition is complete, the mixture is boiled for a further 3 hours. After cooling overnight, the precipitated solid is filtered off with suction and washed with cold ether. The magnesium complex filtered off is hydrolyzed in a solution of 15 g of ammonium chloride in 250 ml of ice water. After 1 hour, the 9-(2-biphenylyl)-2,7-dibromo-9-fluorenol formed is filtered off with suction, washed with water and sucked dry. For the ring-closure reaction, the dried fluorenol is boiled in 100 ml of glacial acetic acid for 6 hours, after addition of 3 drops of concentrated HCl. The mixture is allowed to crystallize overnight, the product formed is filtered off with suction and is washed with glacial acetic acid and water. is added dropwise over a period of 2 hours After the addition After cooling overnight the precipitated solid is filtered off with suction washed with cold ether The magnesium complex filtered off After 1 hour

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3,6-diazabicyclo[3.2.0]heptane-6-carboxylic acid tert-butyl ester (600 mg, 3.0 mmol; prepared according to patent WO2001081347), 2,7-dibromo-fluoren-9-one (1.3 g, 4 mmol; Aldrich), sodium tert-butoxide (400 mg, 4.2 mmol; Aldrich), tris(dibenzylideneacetone)dipalladium (Pd2(dba)3; 160 mg, 0.17 mmol; Alfa) and racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP; 330 mg, 0.53 mmol; Strem) in dry toluene (30 mL) was warmed to 85° C. and stirred under nitrogen atmosphere for 3 h. The reaction mixture was concentrated under vacuum and purified by flash chromatography (80 g silica gel, 40:60 hexanes-EtOAc) to afford the title compound (800 mg, 1.76 mmol; 55% yield): 1H NMR (300 MHz, CD3OD) δ ppm 7.56-7.61 (2H, m), 7.47 (1H, d, J=8 Hz), 7.38 (1H, d, J=8 Hz), 7.06 (1H, d, J=3 Hz), 6.92 (1H, dd, J=8, 3 Hz), 4.60-4.67 (1H, m), 3.91-4.16 (2H, m), 3.73-3.86 (1H, m), 3.55-3.66 (1H, m), 3.41-3.51 (1H, m), 2.90-3.27 (3H, m), 1.36-1.55 (9H, s); MS (DCl/NH3): m/z 455 (M+1)+, 457 (M+3)+. The reaction mixture was concentrated under vacuum purified by flash chromatography (80 g silica gel, 40:60 hexanes-EtOAc)

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3,6-diazabicyclo[3.2.0]heptane-6-carboxylic acid tert-butyl ester (600 mg, 3.0 mmol; prepared according to patent WO2001081347), 2,7-dibromo-fluoren-9-one (1.3 g, 4 mmol; Aldrich), sodium tert-butoxide (400 mg, 4.2 mmol; Aldrich), tris(dibenzylideneacetone)dipalladium (Pd2(dba)3; 160 mg, 0.17 mmol; Alfa) and racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP; 330 mg, 0.53 mmol; Strem) in dry toluene (30 mL) was warmed to 85° C. and stirred under nitrogen atmosphere for 3 h. The reaction mixture was concentrated under vacuum and purified by flash chromatography (80 g silica gel, 40:60 hexanes-EtOAc) to afford the title compound (800 mg, 1.76 mmol; 55% yield): 1H NMR (300 MHz, CD3OD) δ ppm 7.56-7.61 (2H, m), 7.47 (1H, d, J=8 Hz), 7.38 (1H, d, J=8 Hz), 7.06 (1H, d, J=3 Hz), 6.92 (1H, dd, J=8, 3 Hz), 4.60-4.67 (1H, m), 3.91-4.16 (2H, m), 3.73-3.86 (1H, m), 3.55-3.66 (1H, m), 3.41-3.51 (1H, m), 2.90-3.27 (3H, m), 1.36-1.55 (9H, s); MS (DCl/NH3): m/z 455 (M+1)+, 457 (M+3)+. The reaction mixture was concentrated under vacuum purified by flash chromatography (80 g silica gel, 40:60 hexanes-EtOAc)

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-Boc-3,7-diazabicyclo[3.3.0]octane (2.12 g, 10.0 mmol; see WO 0181347), 2,7-dibromofluoren-9-one (6.76 g, 20.0 mmol; Aldrich), tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3; 185 mg, 0.202 mmol; Strem), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP; 310 mg, 0.498 mmol; Strem) and sodium tert-butoxide (1.4 g, 14.6 mmol; Aldrich) in 100 mL toluene was warmed to 85° C. and stirred for 9 h. The reaction mixture was cooled to ambient temperature and filtered through diatomaceous earth, rinsing with dichloromethane. After concentrating the solution under reduced pressure, the residue was purified by column chromatography (silica gel, 10-60% EtOAc/hexanes) to give the title compound (3.54 g, 7.55 mmol, 75% yield). MS (DCl/NH3): m/z 469, 471 (M+1)+. The reaction mixture was cooled to ambient temperature filtered through diatomaceous earth rinsing with dichloromethane After concentrating the solution under reduced pressure the residue was purified by column chromatography (silica gel, 10-60% EtOAc/hexanes)

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-Boc-3,7-diazabicyclo[3.3.0]octane (2.12 g, 10.0 mmol; see WO 0181347), 2,7-dibromofluoren-9-one (6.76 g, 20.0 mmol; Aldrich), tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3; 185 mg, 0.202 mmol; Strem), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP; 310 mg, 0.498 mmol; Strem) and sodium tert-butoxide (1.4 g, 14.6 mmol; Aldrich) in 100 mL toluene was warmed to 85° C. and stirred for 9 h. The reaction mixture was cooled to ambient temperature and filtered through diatomaceous earth, rinsing with dichloromethane. After concentrating the solution under reduced pressure, the residue was purified by column chromatography (silica gel, 10-60% EtOAc/hexanes) to give the title compound (3.54 g, 7.55 mmol, 75% yield). MS (DCl/NH3): m/z 469, 471 (M+1)+. The reaction mixture was cooled to ambient temperature filtered through diatomaceous earth rinsing with dichloromethane After concentrating the solution under reduced pressure the residue was purified by column chromatography (silica gel, 10-60% EtOAc/hexanes)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,7-dibromofluoren-9-one (1.00 g, 2.97 mmol; Aldrich), 3-diethylamino-1-propyne (1.6 mL, 11.6 mmol; Lancaster), triethylamine (2 mL, 14.4 mmol; Acros), dichlorobis(triphenylphosphino)palladium(II) (Cl2Pd(PPh3)2; 90 mg, 0.13 mmol; Aldrich), and copper(I) iodide (130 mg, 0.68 mmol; Aldrich) in DMF (30 mL) was heated to 65° C. for 60 h. The reaction mixture was diluted with EtOAc, washed with water and brine, and dried over Na2SO4. The residue was purified twice by chromatography (80 g silica gel, eluting with 2-7% of 10% NH4OH/MeOH in CH2Cl2, followed by 80 g silica gel, 1-6% MeOH-CH2Cl2) to afford the title compound (1.12 g, 2.81 mmol, 95% yield). MS (DCl/NH3) m/z 399 (M+H)+. washed with water and brine dried over Na2SO4 The residue was purified twice by chromatography (80 g silica gel, eluting with 2-7% of 10% NH4OH/MeOH in CH2Cl2, followed by 80 g silica gel, 1-6% MeOH-CH2Cl2)

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

Procedure: A Grignard reagent prepared from 0.72 g (30 mmol) of magnesium turnings and 5.1 ml (30 mmol) of 2-bromobiphenyl in 15 ml of diethyl ether was added dropwise to a boiling suspension of 10.0 g (29.6 mmol) of 2,7-dibromo-9-fluorenone in 100 ml of dry diethyl ether with stirring (in an ultrasound bath) over the course of 2 h. When addition is complete, the mixture is boiled for a further 3 hours. After cooling overnight, the precipitate which had formed was filtered off with suction and washed with cold ether. The magnesium complex which had been filtered off with suction was hydrolyzed in a solution of 15 g of ammonium chloride in 250 ml of iced water. After 1 h, the 9-(2-biphenylyl)-2,7-dibromo-9-fluorenol which formed was filtered off with suction, washed with water and was sucked dry. For the ring-closure reaction, the dried fluorenol was boiled for 6 hours in 100 ml of glacial acetic acid, after the additon of 3 drops of conc. HCl. The mixture was left to crystallize overnight, and the product which formed was filtered off with suction and washed with glacial acetic acid and water. When addition the mixture is boiled for a further 3 hours After cooling overnight the precipitate which had formed was filtered off with suction washed with cold ether The magnesium complex which had been filtered off with suction After 1 h