N-[4-bromo-2-(trifluoromethyl)phenyl]acetamide

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A suspension of N-(4-bromo-2-trifluoromethyl-phenyl)-acetamide (2.41 g, 8.54 mmol) in acetonitrile (40 mL) was treated with methylene chloride (5 mL) to obtain a clear solution at 25° C. The resulting solution was treated with sodium azide (1.24 g, 19.1 mmol), and the reaction mixture was then cooled to 0° C. The reaction mixture was then treated with trifluoromethanesulfonic anhydride (3.59 g, 12.7 nmmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred overnight, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was then concentrated in vacuo. The resulting residue was diluted with ethyl acetate (50 mL) and water (50 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×30 mL). The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 2/1 hexanes/ethyl acetate) afforded 1-(4-bromo-2-trifluoromethyl-phenyl)-5-methyl-1H-tetrazole (1.85 g, 70%) as a white solid: EI-HRMS m/e calcd for C9H6BrF3N4 (M+) 305.9728, found 305.9733. to obtain a clear solution at 25° C The resulting reaction mixture to warm to 25° C. where it The reaction mixture was then concentrated in vacuo The resulting residue was diluted with ethyl acetate (50 mL) and water (50 mL) The two layers were separated the aqueous layer was extracted with ethyl acetate (1×30 mL) The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

実験手順: A solution of 2-(trifluoromethyl)-4-bromoaniline (4.8 g, 20 mmol) in dry tetrahydrofuran (20 mL) was cooled to 0° C. and then treated with acetic anhydride (8.2 g, 80 mmol). The reaction mixture was stirred at 0° C. for 10 min and then allowed to warm to 25° C. The reaction mixture was stirred at 25° C. for 2 h, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was then concentrated in vacuo. The crude residue precipitated from diethyl ether (50 mL) and hexanes (50 mL). The solid was collected by filtrated and washed with hexanes to afford N-(4-bromo-2-trifluoromethyl-phenyl)-acetamide (5.07 g, 90%) as an amorphous white solid: EI-HRMS m/e calcd for C9H7BrF3NO (M+) 281.8352, found 281.8348. to warm to 25° C The reaction mixture was stirred at 25° C. for 2 h, at which time, thin layer chromatography analysis of the reaction mixture The reaction mixture was then concentrated in vacuo The crude residue precipitated from diethyl ether (50 mL) and hexanes (50 mL) The solid was collected by filtrated washed with hexanes

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

実験手順: A solution of 2-(trifluoromethyl)-4-bromoaniline (4.8 g, 20 mmol) in dry tetrahydrofuran (20 mL) was cooled to 0° C. and then treated with acetic anhydride (8.2 g, 80 mmol). The reaction mixture was stirred at 0° C. for 10 min and then allowed to warm to 25° C. The reaction mixture was stirred at 25° C. for 2 h, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was then concentrated in vacuo. The crude residue precipitated from diethyl ether (50 mL) and hexanes (50 mL). The solid was collected by filtrated and washed with hexanes to afford N-(4-bromo-2-trifluoromethyl-phenyl)-acetamide (5.07 g, 90%) as an amorphous white solid: EI-HRMS m/e calcd for C9H7BrF3NO (M+) 281.8352, found 281.8348. to warm to 25° C The reaction mixture was stirred at 25° C. for 2 h, at which time, thin layer chromatography analysis of the reaction mixture The reaction mixture was then concentrated in vacuo The crude residue precipitated from diethyl ether (50 mL) and hexanes (50 mL) The solid was collected by filtrated washed with hexanes

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

実験手順: A suspension of N-(4-bromo-2-trifluoromethyl-phenyl)-acetamide (2.41 g, 8.54 mmol) in acetonitrile (40 mL) was treated with methylene chloride (5 mL) to obtain a clear solution at 25° C. The resulting solution was treated with sodium azide (1.24 g, 19.1 mmol), and the reaction mixture was then cooled to 0° C. The reaction mixture was then treated with trifluoromethanesulfonic anhydride (3.59 g, 12.7 mmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred overnight, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was then concentrated in vacuo. The resulting residue was diluted with ethyl acetate (50 mL) and water (50 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×30 mL). The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 2/1 hexanes/ethyl acetate) afforded 1-(4-bromo-2-trifluoromethyl-phenyl)-5-methyl-1H-tetrazole (1.85 g, 70%) as a white solid: EI-HRMS m/e calcd for C9H6BrF3N4 (M+) 305.9728, found 305.9733. to obtain a clear solution at 25° C The resulting reaction mixture to warm to 25° C. where it The reaction mixture was then concentrated in vacuo The resulting residue was diluted with ethyl acetate (50 mL) and water (50 mL) The two layers were separated the aqueous layer was extracted with ethyl acetate (1×30 mL) The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

実験手順: A suspension of N-(4-bromo-2-trifluoromethyl-phenyl)-acetamide (2.41 g, 8.54 mmol) in acetonitrile (40 mL) was treated with methylene chloride (5 mL) to obtain a clear solution at 25° C. The resulting solution was treated with sodium azide (1.24 g, 19.1 mmol), and the reaction mixture was then cooled to 0° C. The reaction mixture was then treated with trifluoromethanesulfonic anhydride (3.59 g, 12.7 mmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred overnight, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was then concentrated in vacuo. The resulting residue was diluted with ethyl acetate (50 mL) and water (50 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×30 mL). The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 2/1 hexanes/ethyl acetate) afforded 1-(4-bromo-2-trifluoromethyl-phenyl)-5-methyl-1H-tetrazole (1.85 g, 70%) as a white solid: EI-HRMS m/e calcd for C9H6BrF3N4 (M+) 305.9728, found 305.9733. to obtain a clear solution at 25° C The resulting reaction mixture to warm to 25° C. where it The reaction mixture was then concentrated in vacuo The resulting residue was diluted with ethyl acetate (50 mL) and water (50 mL) The two layers were separated the aqueous layer was extracted with ethyl acetate (1×30 mL) The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

実験手順: A solution of 2-(trifluoromethyl)-4-bromoaniline (4.8 g, 20 mmol) in dry tetrahydrofuran (20 mL) was cooled to 0° C. and then treated with acetic anhydride (8.2 g, 80 mmol). The reaction mixture was stirred at 0° C. for 10 min and then allowed to warm to 25° C. The reaction mixture was stirred at 25° C. for 2 h, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was then concentrated in vacuo. The crude residue precipitated from diethyl ether (50 mL) and hexanes (50 mL). The solid was collected by filtrated and washed with hexanes to afford N-(4-bromo-2-trifluoromethyl-phenyl)-acetamide (5.07 g, 90%) as an amorphous white solid: EI-HRMS m/e calcd for C9H7BrF3NO (M+) 281.8352, found 281.8348. to warm to 25° C The reaction mixture was stirred at 25° C. for 2 h, at which time, thin layer chromatography analysis of the reaction mixture The reaction mixture was then concentrated in vacuo The crude residue precipitated from diethyl ether (50 mL) and hexanes (50 mL) The solid was collected by filtrated washed with hexanes

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

実験手順: A suspension of N-(4-bromo-2-trifluoromethyl-phenyl)-acetamide (2.41 g, 8.54 mmol) in acetonitrile (40 mL) was treated with methylene chloride (5 mL) to obtain a clear solution at 25° C. The resulting solution was treated with sodium azide (1.24 g, 19.1 mmol), and the reaction mixture was then cooled to 0° C. The reaction mixture was then treated with trifluoromethanesulfonic anhydride (3.59 g, 12.7 mmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred overnight, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was then concentrated in vacuo. The resulting residue was diluted with ethyl acetate (50 mL) and water (50 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×30 mL). The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 2/1 hexanes/ethyl acetate) afforded 1-(4-bromo-2-trifluoromethyl-phenyl)-5-methyl-1H-tetrazole (1.85 g, 70%) as a white solid: EI-HRMS m/e calcd for C9H6BrF3N4 (M+) 305.9728, found 305.9733. to obtain a clear solution at 25° C The resulting reaction mixture to warm to 25° C. where it The reaction mixture was then concentrated in vacuo The resulting residue was diluted with ethyl acetate (50 mL) and water (50 mL) The two layers were separated the aqueous layer was extracted with ethyl acetate (1×30 mL) The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

実験手順: A suspension of N-(4-bromo-2-trifluoromethyl-phenyl)-acetamide (2.41 g, 8.54 mmol) in acetonitrile (40 mL) was treated with methylene chloride (5 mL) to obtain a clear solution at 25° C. The resulting solution was treated with sodium azide (1.24 g, 19.1 mmol), and the reaction mixture was then cooled to 0° C. The reaction mixture was then treated with trifluoromethanesulfonic anhydride (3.59 g, 12.7 mmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred overnight, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was then concentrated in vacuo. The resulting residue was diluted with ethyl acetate (50 mL) and water (50 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×30 mL). The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 2/1 hexanes/ethyl acetate) afforded 1-(4-bromo-2-trifluoromethyl-phenyl)-5-methyl-1H-tetrazole (1.85 g, 70%) as a white solid: EI-HRMS m/e calcd for C9H6BrF3N4 (M+) 305.9728, found 305.9733. to obtain a clear solution at 25° C The resulting reaction mixture to warm to 25° C. where it The reaction mixture was then concentrated in vacuo The resulting residue was diluted with ethyl acetate (50 mL) and water (50 mL) The two layers were separated the aqueous layer was extracted with ethyl acetate (1×30 mL) The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

実験手順: A solution of 2-(trifluoromethyl)-4-bromoaniline (4.8 g, 20 mmol) in dry tetrahydrofuran (20 mL) was cooled to 0° C. and then treated with acetic anhydride (8.2 g, 80 mmol). The reaction mixture was stirred at 0° C. for 10 min and then allowed to warm to 25° C. The reaction mixture was stirred at 25° C. for 2 h, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was then concentrated in vacuo. The crude residue precipitated from diethyl ether (50 mL) and hexanes (50 mL). The solid was collected by filtrated and washed with hexanes to afford N-(4-bromo-2-trifluoromethyl-phenyl)-acetamide (5.07 g, 90%) as an amorphous white solid: EI-HRMS m/e calcd for C9H7BrF3NO (M+) 281.8352, found 281.8348. to warm to 25° C The reaction mixture was stirred at 25° C. for 2 h, at which time, thin layer chromatography analysis of the reaction mixture The reaction mixture was then concentrated in vacuo The crude residue precipitated from diethyl ether (50 mL) and hexanes (50 mL) The solid was collected by filtrated washed with hexanes

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

実験手順: A suspension of N-(4-bromo-2-trifluoromethyl-phenyl)-acetamide (2.41 g, 8.54 mmol) in acetonitrile (40 mL) was treated with methylene chloride (5 mL) to obtain a clear solution at 25° C. The resulting solution was treated with sodium azide (1.24 g, 19.1 mmol), and the reaction mixture was then cooled to 0° C. The reaction mixture was then treated with trifluoromethanesulfonic anhydride (3.59 g, 12.7 mmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred overnight, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was then concentrated in vacuo. The resulting residue was diluted with ethyl acetate (50 mL) and water (50 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×30 mL). The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 2/1 hexanes/ethyl acetate) afforded 1-(4-bromo-2-trifluoromethyl-phenyl)-5-methyl-1H-tetrazole (1.85 g, 70%) as a white solid: EI-HRMS m/e calcd for C9H6BrF3N4 (M+) 305.9728, found 305.9733. to obtain a clear solution at 25° C The resulting reaction mixture to warm to 25° C. where it The reaction mixture was then concentrated in vacuo The resulting residue was diluted with ethyl acetate (50 mL) and water (50 mL) The two layers were separated the aqueous layer was extracted with ethyl acetate (1×30 mL) The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

実験手順: A solution of 2-(trifluoromethyl)-4-bromoaniline (4.8 g, 20 mmol) in dry tetrahydrofuran (20 mL) was cooled to 0° C. and then treated with acetic anhydride (8.2 g, 80 mmol). The reaction mixture was stirred at 0° C. for 10 min and then allowed to warm to 25° C. The reaction mixture was stirred at 25° C. for 2 h, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was then concentrated in vacuo. The crude residue precipitated from diethyl ether (50 mL) and hexanes (50 mL). The solid was collected by filtration and washed with hexanes to afford N-(4-bromo-2-trifluoromethyl-phenyl)-acetamide (5.07 g, 90%) as an amorphous white solid: EI-HRMS m/e calcd for C9H7BrF3NO (M+) 281.8352, found 281.8348. to warm to 25° C The reaction mixture was stirred at 25° C. for 2 h, at which time, thin layer chromatography analysis of the reaction mixture The reaction mixture was then concentrated in vacuo The crude residue precipitated from diethyl ether (50 mL) and hexanes (50 mL) The solid was collected by filtration washed with hexanes