5-Chloro-2-fluorobenzenesulfonyl chloride

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

実験手順: A solution of 5-chloro-2-fluorobenzene-1-sulfonyl chloride (2.0 g) in tetrahydrofuran (30 ml) was added to a solution of tert-butylamine (9.15 ml) in tetrahydrofuran (70 ml) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The precipitate was removed by filtration and the filtrate was concentrated in vacuo to give N-tert-butyl-5-chloro-2-fluoro-benzenesulfonamide (2.2 g, 95% yield) as a white solid. The precipitate was removed by filtration the filtrate was concentrated in vacuo

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Aminomethyl-N-tert-butyl-2-fluoro-benzenesulfonamide was synthesized in a manner analogous to 4-Aminomethyl-N-tert-butyl-3-methyl-benzenesulfonamide in Example 4, using 5-chloro-2-fluorobenzene-1-sulfonyl chloride in place of 4-bromo-3-methylbenzene-1-sulfonyl chloride. In the second step NMP was used as the solvent, Pd(dppf)Cl2 alone was used as catalyst and the reaction mixture was stirred at 120° C. for 15 hours.

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: 5-Chloro-2-fluoro-benzenesulfonyl chloride (10.5 g) and 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (10.0 g) were added to a reaction vessel containing a magnetic stirring bar, followed by 200 ml dry DCM and 4.1 ml pyridine. The reaction mixture was stirred at RT for 20 h before being cooled on an ice-bath and quenched with 1M aqueous sodium hydroxide solution. The organic phase was separated and the aqueous phase acidified with 2M aqueous hydrochloric acid and extracted three times with EtOAc. The combined organic phases were washed with brine and dried over sodium sulfate and evaporated to afford the crude product. Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent afforded the title compound as a colorless solid after evaporation of the solvents under reduced pressure. Yield: 14.14 g (75%). containing a magnetic stirring bar before being cooled on an ice-bath quenched with 1M aqueous sodium hydroxide solution The organic phase was separated extracted three times with EtOAc The combined organic phases were washed with brine dried over sodium sulfate evaporated to afford the crude product Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent

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

実験手順: 5-Chloro-2-fluoro-benzenesulfonyl chloride (10.5 g) and 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (10.0 g) were added to a reaction vessel containing a magnetic stirring bar, followed by 200 ml dry DCM and 4.1 ml pyridine. The reaction mixture was stirred at RT for 20 h before being cooled on an ice-bath and quenched with 1M aqueous sodium hydroxide solution. The organic phase was separated and the aqueous phase acidified with 2M aqueous hydrochloric acid and extracted three times with EtOAc. The combined organic phases were washed with brine and dried over sodium sulfate and evaporated to afford the crude product. Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent afforded the title compound as a colorless solid after evaporation of the solvents under reduced pressure. Yield: 14.14 g (75%). containing a magnetic stirring bar before being cooled on an ice-bath quenched with 1M aqueous sodium hydroxide solution The organic phase was separated extracted three times with EtOAc The combined organic phases were washed with brine dried over sodium sulfate evaporated to afford the crude product Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent

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

実験手順: A solution of 5-chloro-2-fluorobenzene-1-sulfonyl chloride (2.0 g) in tetrahydrofuran (30 ml) was added to a solution of tert-butylamine (9.15 ml) in tetrahydrofuran (70 ml) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The precipitate was removed by filtration and the filtrate was concentrated in vacuo to give N-tert-butyl-5-chloro-2-fluoro-benzenesulfonamide (2.2 g, 95% yield) as a white solid. The precipitate was removed by filtration the filtrate was concentrated in vacuo

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Aminomethyl-N-tert-butyl-2-fluoro-benzenesulfonamide was synthesized in a manner analogous to 4-Aminomethyl-N-tert-butyl-3-methyl-benzenesulfonamide in Example 4, using 5-chloro-2-fluorobenzene-1-sulfonyl chloride in place of 4-bromo-3-methylbenzene-1-sulfonyl chloride. In the second step NMP was used as the solvent, Pd(dppf)Cl2 alone was used as catalyst and the reaction mixture was stirred at 120° C. for 15 hours.

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: A solution of 5-chloro-2-fluorobenzene-1-sulfonyl chloride (2.0 g) in tetrahydrofuran (30 ml) was added to a solution of tert-butylamine (9.15 ml) in tetrahydrofuran (70 ml) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The precipitate was removed by filtration and the filtrate was concentrated in vacuo to give N-tert-butyl-5-chloro-2-fluoro-benzenesulfonamide (2.2 g, 95% yield) as a white solid. The precipitate was removed by filtration the filtrate was concentrated in vacuo

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Aminomethyl-N-tert-butyl-2-fluoro-benzenesulfonamide was synthesized in a manner analogous to 4-Aminomethyl-N-tert-butyl-3-methyl-benzenesulfonamide in Example 4, using 5-chloro-2-fluorobenzene-1-sulfonyl chloride in place of 4-bromo-3-methylbenzene-1-sulfonyl chloride. In the second step NMP was used as the solvent, Pd(dppf)Cl2 alone was used as catalyst and the reaction mixture was stirred at 120° C. for 15 hours.

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

実験手順: 5-Chloro-2-fluoro-benzenesulfonyl chloride (10.5 g) and 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (10.0 g) were added to a reaction vessel containing a magnetic stirring bar, followed by 200 ml dry DCM and 4.1 ml pyridine. The reaction mixture was stirred at RT for 20 h before being cooled on an ice-bath and quenched with 1M aqueous sodium hydroxide solution. The organic phase was separated and the aqueous phase acidified with 2M aqueous hydrochloric acid and extracted three times with EtOAc. The combined organic phases were washed with brine and dried over sodium sulfate and evaporated to afford the crude product. Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent afforded the title compound as a colorless solid after evaporation of the solvents under reduced pressure. Yield: 14.14 g (75%). containing a magnetic stirring bar before being cooled on an ice-bath quenched with 1M aqueous sodium hydroxide solution The organic phase was separated extracted three times with EtOAc The combined organic phases were washed with brine dried over sodium sulfate evaporated to afford the crude product Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent