2-(4-bromophenyl)benzonitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Combine 2-iodobenzonitrile (9.0 g, 38.5 mmol), 4-bromophenylboronic acid (10.4 g, 51.8 mmol), 2M aqueous sodium carbonate (20 mL) and tetrakis(triphenylphosphine)-palladium(0) (4.5 g, 3.9 mmol) in 300 mL of dioxane and heat to 80° C. under nitrogen with stirring. After 3 hours cool to room temperature and dilute with 900 mL of ethyl acetate. Wash with water (2×50 mL), brine (1×50 mL) and dry over sodium sulfate. Filter and evaporate to a yellow solid. Chromatograph on silica gel two times, eluting with a gradient of 100% toluene to 1/9 ethyl acetate/toluene to give the title compound as a tan solid, 5.42 g (55%). MS (FAB)=257 (M+); HPLC analysis is 95%. Wash with water (2×50 mL), brine (1×50 mL) dry over sodium sulfate Filter evaporate to a yellow solid Chromatograph on silica gel two times, eluting with a gradient of 100% toluene to 1/9 ethyl acetate/toluene

反応条件: temp:3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add 2-(4-bromophenyl)benzamide (12.0 g, 0.04345 moles, preparation 60), acetonitrile (120 mL), and triethylamine (9.23 grams, 0.0912 moles) to a 250 mL 3-neck round-bottom flask equipped with a magnetic stirrer, internal temperature probe, ice-water bath, and addition funnel. Cool the contents of the 250 mL 3-neck round-bottom flask to 3° C. Add trifluoroacetic anhydride (9.6 grams, 0.0456 moles) to the reaction mixture via the addition funnel over 5 minutes. The reaction mixture warms to 12-15° C. Remove the ice-water bath, and allow the reaction mixture to warm to 20° C. and stir the mixture for 45 minutes. Add additional trifluoroacetic anhydride (0.8 g, 0.0038 moles) and stir the reaction mixture at 22° C. for 75 minutes. Add water (120 mL) and cool the resulting suspension to 3° C. Stir the suspension at 3° C. for 15 minutes. Collect the precipitate by filtration and rinse the filter cake three times with 15 mL of 30% acetonitrile and 70% water. Vacuum (15-25 mm) dry the filter cake at 45° C. to provide the title compound (10.6 g, 0.041 moles) in 94.5% yield. 1H NMR (CDCl3, 500.0 MHz): δ 7.75 (app. d, 1H, J=8); 7.64 (td, 1H, J=1.5, 7.5); 7.61 (app. d, 2H, J=8.5); 7.5-7.4 (m, 4H). equipped with a magnetic stirrer warms to 12-15° C Remove the ice-water bath to warm to 20° C. stir the reaction mixture at 22° C. for 75 minutes Stir the suspension at 3° C. for 15 minutes Collect the precipitate by filtration rinse the filter cake three times with 15 mL of 30% acetonitrile and 70% water Vacuum (15-25 mm) dry the filter cake at 45° C.

反応条件: temp:-73.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add 2-(4-bromophenyl)benzenecarbonitrile (1.29 g, 0.005 moles, preparation 61), tetrahydrofuran (52 mL), and triisopropyl borate (2.82 grams, 0.015 moles) to a 100 mL 3-neck round-bottom flask equipped with a magnetic stirrer, internal temperature probe, dry ice-acetone bath, and addition funnel. Stir the mixture under nitrogen and cool the contents of the 100 mL 3-neck round-bottom flask to −73° C. Transfer a solution of n-butyl lithium 1.6 M in hexanes (8.7 mL, 0.0139 moles) via cannula to the addition funnel. Add n-butyl lithium (4.7 mL, 0.0075 moles) to the reaction mixture over 7 minutes while maintaining −65 to −73° C. Slowly warm the reaction mixture to −15° C. Cool the reaction mixture to −70° C. Add n-butyl lithium (3.0 mL, 0.0048 moles) to the reaction mixture dropwise. Slowly warm the reaction mixture to −15° C. Cool the reaction mixture to −60° C. Add n-butyl lithium (1.0 mL, 0.0016 moles) to the reaction mixture dropwise. Slowly warm the reaction mixture to −15° C. Cool the reaction mixture to −30° C. Add 1.0 N hydrochloric acid (20 mL, 0.02 moles). Remove the dry ice-acetone bath, and allow the reaction mixture to warm to 23° C. Transfer the reaction m mixture to a separatory funnel. Separate the phases and concentrate the organic phase to a solid under reduced pressure (15-25 mm). Add water (50 mL), 5N NaOH until pH 11.5 is observed, dichloromethane (40 mL), and tetrahydrofuran (20 mL). Transfer the reaction mixture to a separatory funnel and separate the phases. Acidify the aqueous phase and concentrate the suspension under reduced pressure (15-25 mm) to remove residual organic solvents. Collect the precipitate by filtration. Vacuum (15-25 mm) dry the filter cake at 45° C. to provide the title compound (0.30 g, 0.0013 moles) in 26.9% yield. 1H NMR (DMSO-d6, 500.0 MHz): δ 8.21 (s, 2H); 7.98 (dd, 1H, J=1.5, 8); 7.95 (d, 2H, J=8); 7.82 (dt, 1H, J=1.5, 7.5); 7.66 (d, 1H, J=7); 7.61 (dt, 1H, J=1, 8); 7.57 (d, 2H, J=8). equipped with a magnetic stirrer Slowly warm the reaction mixture to −15° C Cool the reaction mixture to −70° C Slowly warm the reaction mixture to −15° C Cool the reaction mixture to −60° C Slowly warm the reaction mixture to −15° C Cool the reaction mixture to −30° C Remove the dry ice-acetone bath to warm to 23° C Separate the phases concentrate the organic phase to a solid under reduced pressure (15-25 mm) Transfer the reaction mixture to a separatory funnel and separate the phases concentrate the suspension under reduced pressure (15-25 mm) to remove residual organic solvents Collect the precipitate by filtration Vacuum (15-25 mm) dry the filter cake at 45° C.

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dry THF (4 mL) is cooled to at −3° C. under nitrogen. BuMgCl (0.6 mL, 1.2 mmol, 2M in THF) is added. n-BuLi (1.5 mL, 2.4 mmol, 1.6 M in hexanes) is then added dropwise over 20 min at −3° C. to 0° C. After the addition, the solution is stirred at 0° C. for 45 min. The solution is cooled to −45° C. and treated dropwise over 20 min at −45 to −40° C. with a solution of 2-(4-bromophenyl)benzenecarbonitrile (0.5 g, 1.9 mmol) in a total of 4 mL THF. The resulting yellowish-orange solution is allowed to warm to −25° C. over 1 h. After 1 h, the solution is cooled to −73° C. Trimethylborate (0.43 mL, 3.87 mmol) is added dropwise over 15 min at −73° C. The solution is stirred 1 h at −73° C. The reaction is allowed to warm to −63° C. The reaction is quenched with 5 mL of 1N HCl and allowed to warm to 0° C. with stirring. The mixture is extracted with 10 mL ethyl acetate. The organic solution is shaken with brine, dried (Na2SO4).and concentrated to obtain 0.435 g of crude product. This in 5 mL of 1:1 toluene/heptane is heated to 95° C. with stirring for 10 min. Upon cooling to rt and then to 10° C., the solid is collected by filtration and rinsed three times 1:1 toluene/heptane. The solid is vacuum-dried to provide title compound (0.232 g, 95.65% HPLC, Hitachi 7000 series, SB phenyl column, 218 nm, 65% MeCN/35% water with 0.05% TFA, 1 mL/min). After the addition The solution is cooled to −45° C. to warm to −25° C. over 1 h After 1 h the solution is cooled to −73° C The solution is stirred 1 h at −73° C to warm to −63° C The reaction is quenched with 5 mL of 1N HCl to warm to 0° C. with stirring The mixture is extracted with 10 mL ethyl acetate The organic solution is shaken with brine dried (Na2SO4) .and concentrated to obtain 0.435 g of crude product with stirring for 10 min Upon cooling to rt to 10° C., the solid is collected by filtration rinsed three times 1:1 toluene/heptane The solid is vacuum-dried