1-benzyl-4-bromobenzene

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

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

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 4 mL vial charged with a stir bar, N-(5-methyl-1,3-thiazol-2-yl)pyrrolidine-1-carboxamide (58 mg, 0.27 mmol) was added, followed by copper(I) trifluoromethanesulfonate benzene complex (27 mg, 0.05 mmol), 5-chloro-1,10-phenanthroline (23 mg, 0.11 mmol) and cesium carbonate (97 mg, 0.3 mmol). A loose cap with septum was placed on the vial, and the vial was placed under vacuum in a vacuum oven for 30 minutes. The solid mixture was purged with nitrogen gas a couple of times. Then, 1-benzyl-4-bromobenzene (74 mg, 0.3 mmol) dissolved in 1-methyl-2-pyrrolidinone (1.0 mL) was added to the mixture. The vial was capped and placed on a heater/stirrer and heated to 120° C. overnight. Then 1 mL of a solution of concentrated ammonium hydroxide/water (1:2) was added. The reaction was filtered and concentrated to dryness. The residue was purified by reverse phase HPLC (C8, gradient 10-100% acetonitrile/water/0.1% trifluoroacetic acid). In a 4 mL vial charged with a stir bar A loose cap with septum The solid mixture was purged with nitrogen gas a couple of times was added to the mixture The vial was capped placed on a heater/stirrer The reaction was filtered concentrated to dryness The residue was purified by reverse phase HPLC (C8, gradient 10-100% acetonitrile/water/0.1% trifluoroacetic acid)

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

Procedure: To a stirred solution of 21 mL (42 mmol, 2.0M in THF) of benzylmagnesium chloride at room temperature under nitrogen was added a solution of 6.80 g (50.0 mmol) of thrice-fused zinc chloride, in 50 mL of THF. The resulting tan slurry was stirred for 1 hour. To this slurry was added 10.0 g (35.3 mmol) 1-bromo-4-iodobenzene and 450 mg (0.4 mmol) of tetrakis(tri-phenylphosphine)palladium in 30 mL of THF. The reaction was stirred at room temperature for 16 hours and then quenched with 50 mL of 2M hydro-chloric acid. The mixture was extracted thrice with hexanes, the extracts combined, washed once with saturated sodium bicarbonate solution and once with 10% sodium thiosulfate. The organic extract was dried (MgSO4) and evaporated. The crude product was purified by flash chromatography on silica gel (5×25 cm column, hexanes as elutent) to give 7.05 g (80%) of title compound as a colorless oil. The reaction was stirred at room temperature for 16 hours quenched with 50 mL of 2M hydro-chloric acid The mixture was extracted thrice with hexanes washed once with saturated sodium bicarbonate solution and once with 10% sodium thiosulfate The organic extract was dried (MgSO4) evaporated The crude product was purified by flash chromatography on silica gel (5×25 cm column, hexanes as elutent)

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

Procedure: To a stirred solution of 21 mL (42 mmol, 2.0M in THF) of benzylmagnesium chloride at room temperature under nitrogen was added a solution of 6.80 g (50.0 mmol) of thrice-fused zinc chloride, in 50 mL of THF. The resulting tan slurry was stirred for 1 hour. To this slurry was added 10.0 g (35.3 mmol) 1-bromo-4-iodobenzene and 450 mg (0.4 mmol) of tetrakis(tri-phenylphosphine)palladium in 30 mL of THF. The reaction was stirred at room temperature for 16 hours and then quenched with 50 mL of 2M hydro-chloric acid. The mixture was extracted thrice with hexanes, the extracts combined, washed once with saturated sodium bicarbonate solution and once with 10% sodium thiosulfate. The organic extract was dried (MgSO4) and evaporated. The crude product was purified by flash chromatography on silica gel (5×25 cm column, hexanes as elutent) to give 7.05 g (80%) of title compound as a colorless oil. The reaction was stirred at room temperature for 16 hours quenched with 50 mL of 2M hydro-chloric acid The mixture was extracted thrice with hexanes washed once with saturated sodium bicarbonate solution and once with 10% sodium thiosulfate The organic extract was dried (MgSO4) evaporated The crude product was purified by flash chromatography on silica gel (5×25 cm column, hexanes as elutent)

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

Procedure: To a stirred solution of 21 mL (42 mmol, 2.0M in THF) of benzylmagnesium chloride at room temperature under nitrogen was added a solution of 6.80 g (50.0 mmol) of thrice-fused zinc chloride in 50 mL of THF. The resulting tan slurry was stirred for 1 hour. To this slurry was added 10.0 g (35.3 mmol) 1-bromo-4-iodobenzene and 450 mg (0.4 mmol) of tetrakis(tri-phenylphosphine)palladium in 30 mL of THF. The reaction was stirred at room temperature for 16 hours and then quenched with 50 mL of 2M hydro-chloric acid. The mixture was extracted thrice with hexanes, the extracts combined, washed once with saturated sodium bicarbonate solution and once with 10% sodium thiosulfate. The organic extract was dried (MgSO4) and evaporated. The crude product was purified by flash chromatography on silica gel (5×25 cm column, hexanes as elutent) to give 7.05 g (80%) of title compound as a colorless oil. The reaction was stirred at room temperature for 16 hours quenched with 50 mL of 2M hydro-chloric acid The mixture was extracted thrice with hexanes washed once with saturated sodium bicarbonate solution and once with 10% sodium thiosulfate The organic extract was dried (MgSO4) evaporated The crude product was purified by flash chromatography on silica gel (5×25 cm column, hexanes as elutent)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 4 mL vial charged with a stir bar, N-(5-methyl-1,3-thiazol-2-yl)pyrrolidine-1-carboxamide (58 mg, 0.27 mmol) was added, followed by copper(I) trifluoromethanesulfonate benzene complex (27 mg, 0.05 mmol), 5-chloro-1,10-phenanthroline (23 mg, 0.11 mmol) and cesium carbonate (97 mg, 0.3 mmol). A loose cap with septum was placed on the vial, and the vial was placed under vacuum in a vacuum oven for 30 minutes. The solid mixture was purged with nitrogen gas a couple of times. Then, 1-benzyl-4-bromobenzene (74 mg, 0.3 mmol) dissolved in 1-methyl-2-pyrrolidinone (1.0 mL) was added to the mixture. The vial was capped and placed on a heater/stirrer and heated to 120° C. overnight. Then 1 mL of a solution of concentrated ammonium hydroxide/water (1:2) was added. The reaction was filtered and concentrated to dryness. The residue was purified by reverse phase HPLC (C8, gradient 10-100% acetonitrile/water/0.1% trifluoroacetic acid). In a 4 mL vial charged with a stir bar A loose cap with septum The solid mixture was purged with nitrogen gas a couple of times was added to the mixture The vial was capped placed on a heater/stirrer The reaction was filtered concentrated to dryness The residue was purified by reverse phase HPLC (C8, gradient 10-100% acetonitrile/water/0.1% trifluoroacetic acid)

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

Procedure: To a stirred solution of 21 mL (42 mmol, 2.0M in THF) of benzylmagnesium chloride at room temperature under nitrogen was added a solution of 6.80 g (50.0 mmol) of thrice-fused zinc chloride in 0 50 mL of THF. The resulting tan slurry was stirred for 1 hour. To this slurry was added 10.0 g (35.3 mmol) 1-bromo-4-iodobenzene and 450 mg (0.4 mmol) of tetrakis(tri-phenylphosphine)palladium in 30 mL of THF. The reaction was stirred at room temperature for 16 hours and then quenched with 50 mL of 2M hydro-chloric acid. The mixture was extracted thrice with hexanes, the extracts combined, washed once with saturated sodium bicarbonate solution and once with 10% sodium thiosulfate. The organic extract was dried (MgSO4) and evaporated. The crude product was purified by flash chromatography on silica gel (5×25 cm column, hexanes as elutent) to give 7.05 g (80%) of title compound as a colorless oil. The reaction was stirred at room temperature for 16 hours quenched with 50 mL of 2M hydro-chloric acid The mixture was extracted thrice with hexanes washed once with saturated sodium bicarbonate solution and once with 10% sodium thiosulfate The organic extract was dried (MgSO4) evaporated The crude product was purified by flash chromatography on silica gel (5×25 cm column, hexanes as elutent)

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

Procedure: To a stirred solution of 21 mL (42 mmol, 2.0M in THF) of benzylmagnesium chloride at room temperature under nitrogen was added a solution of 6.80 g (50.0 mmol) of thrice-fused zinc chloride in 0 50 mL of THF. The resulting tan slurry was stirred for 1 hour. To this slurry was added 10.0 g (35.3 mmol) 1-bromo-4-iodobenzene and 450 mg (0.4 mmol) of tetrakis(tri-phenylphosphine)palladium in 30 mL of THF. The reaction was stirred at room temperature for 16 hours and then quenched with 50 mL of 2M hydro-chloric acid. The mixture was extracted thrice with hexanes, the extracts combined, washed once with saturated sodium bicarbonate solution and once with 10% sodium thiosulfate. The organic extract was dried (MgSO4) and evaporated. The crude product was purified by flash chromatography on silica gel (5×25 cm column, hexanes as elutent) to give 7.05 g (80%) of title compound as a colorless oil. The reaction was stirred at room temperature for 16 hours quenched with 50 mL of 2M hydro-chloric acid The mixture was extracted thrice with hexanes washed once with saturated sodium bicarbonate solution and once with 10% sodium thiosulfate The organic extract was dried (MgSO4) evaporated The crude product was purified by flash chromatography on silica gel (5×25 cm column, hexanes as elutent)

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

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

Procedure: To a round bottom flask containing 1-benzyl-4-bromo-benzene (700 mg, 2.83 mmol) and 5-formyl-2-furan-boronic acid (595 mg, 4.25 mmol) in dimethoxyethane (30 mL) and ethanol (7.5 mL) was added an aqueous solution of sodium carbonate (900 mg, 8.49 mmol) in water (10 mL) The reaction mixture was stirred at room temperature for 5 minutes, followed by the addition of tetrakis(triphenylphosphine)palladium (162 mg, 0.14 mmol). The reaction was heated at 70° C. for 1 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (200 mL) and water (20 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with brine, dried (sodium sulfate) and concentrated under vacuum. The crude product was purified by silica gel chromatography eluting with 6% ethyl acetate in hexanes to afford 5-(4-benzyl-phenyl)-furan-2-carbaldehyde (320 mg g, 43%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ 3.99 (2H, s), 7.20-7.39 (8H, m), 7.63 (1H, d, J=3.6 Hz), 7.78-7.81 (2H, m), 9.59 (1H, s); APCI-MS: 262.02. The reaction was heated at 70° C. for 1 h The reaction mixture was cooled to room temperature The layers were separated the aqueous layer was extracted with ethyl acetate (2×50 mL) The combined organic extracts were washed with brine dried (sodium sulfate) concentrated under vacuum The crude product was purified by silica gel chromatography eluting with 6% ethyl acetate in hexanes

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

Procedure: α,α′-Diphenyl-α-hydroxyl-p-xylene was prepared as shown in Scheme 4 by using 29.0 g (117 mmol) of 4-bromo diphenylmethane and 11.2 g (106 mmol) of benzaldehyde/19.7 g (106 mmol) by the similar procedure to the method for preparing 4-bromobenzhydrol. The crude product was dissolved in chloroform and filtered through G60 column filled with silica gel. After evaporating the solvent, the result product was recrystallized with hexane/chloroform (9:1 v/v) to provide a yield of 86%. MP: 64° C. filtered through G60 column filled with silica gel After evaporating the solvent the result product was recrystallized with hexane/chloroform (9:1 v/v) to provide a yield of 86%