2-甲基-1-甲巯基-2-丙胺

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Sodium hydroxide (0.83 g) and sodium hydrogencarbonate (1.66 g) were dissolved in water (12 mL), followed by adding thereto 2-methyl-1-methylthio-2-propanamine (2.62 g) and chlorobenzene (12 mL), and to the resulting mixture was added dropwise phthaloyl dichloride (4 g) at 40° C. or lower. After completion of the dropwise addition, the resulting mixture was stirred at 40° C. for 30 minutes and sodium chloride (1.73 g) was added thereto. Thereafter, the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in chlorobenzene. The previously prepared isophthalimide solution and 15% hydrogen peroxide (4.9 g) were alternately and slowly dropped into a mixture of 2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]aniline (5.15 g), p-toluenesulfonic acid monohydrate (0.09 g) and chlorobenzene (3 mL) at 50° C. and then stirred at 60° C. for 3 hours. An aqueous sodium sulfite solution was added dropwise to the thus obtained reaction mixture at the same temperature to decompose the excess oxidizing agent. After neutralization with an aqueous sodium hydrogencarbonate solution, the resulting mixture was slowly cooled to 20° C. The crystals precipitated were filtered, washed with water and then dried to obtain 9.06 g (yield 85%) of the title compound. by adding After completion of the dropwise addition Thereafter, the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in chlorobenzene stirred at 60° C. for 3 hours The crystals precipitated were filtered washed with water dried

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Sodium hydroxide (0.83 g) and sodium hydrogencarbonate (1.66 g) were dissolved in water (12 mL), followed by adding thereto 2-methyl-1-methylthio-2-propanamine (2.62 g) and chlorobenzene (12 mL), and to the resulting mixture was added dropwise phthaloyl dichloride (4 g) at 40° C. or lower. After completion of the dropwise addition, the resulting mixture was stirred at 40° C. for 30 minutes and sodium chloride (1.73 g) was added thereto. Thereafter, the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in chlorobenzene. The previously prepared isophthalimide solution and 15% hydrogen peroxide (4.9 g) were alternately and slowly dropped into a mixture of 2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]aniline (5.15 g), p-toluenesulfonic acid monohydrate (0.09 g) and chlorobenzene (3 mL) at 50° C. and then stirred at 60° C. for 3 hours. An aqueous sodium sulfite solution was added dropwise to the thus obtained reaction mixture at the same temperature to decompose the excess oxidizing agent. After neutralization with an aqueous sodium hydrogencarbonate solution, the resulting mixture was slowly cooled to 20° C. The crystals precipitated were filtered, washed with water and then dried to obtain 9.06 g (yield 85%) of the title compound. by adding After completion of the dropwise addition Thereafter, the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in chlorobenzene stirred at 60° C. for 3 hours The crystals precipitated were filtered washed with water dried

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Sodium hydroxide (17.78 g) and sodium hydrogencarbonate (35.57 g) were dissolved in water (253 mL), followed by adding thereto 2-methyl-1-methylthio-2-propanamine (53 g) and 1,2-dichloroethane (253 mL), and to the resulting mixture was added dropwise phthaloyl dichloride (85.95 g) at 40° C. or lower. After completion of the dropwise addition, the resulting mixture was stirred at 40° C. for 30 minutes and the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane. The previously prepared isophthalimide solution and 35% hydrogen peroxide (45.27 g) were slowly dropped at the same time into a mixture of 2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-aniline (110.7 g), p-toluenesulfonic acid monohydrate (2.01 g) and 1,2-dichloroethane (40 mL) at 60° C. and then stirred at 60° C. for 3 hours. An aqueous sodium sulfite solution was added dropwise to the thus obtained reaction mixture at the same temperature to decompose the excess oxidizing agent. Then, the resulting mixture was neutralized with an aqueous sodium hydrogencarbonate solution, after which the organic layer was separated. The organic layer obtained was slowly cooled to 20° C. The crystals precipitated were filtered, washed with water and then dried to obtain 184.11 g (yield 80%) of the title compound. by adding After completion of the dropwise addition the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane stirred at 60° C. for 3 hours after which the organic layer was separated The organic layer obtained was slowly cooled to 20° C The crystals precipitated were filtered washed with water dried

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Sodium hydroxide (0.83 g) and sodium hydrogencarbonate (1.66 g) were dissolved in water (12 mL), followed by adding thereto 2-methyl-1-methylthio-2-propanamine (2.62 g) and chlorobenzene (12 mL), and to the resulting mixture was added dropwise phthaloyl dichloride (4 g) at 40° C. or lower. After completion of the dropwise addition, the resulting mixture was stirred at 40° C. for 30 minutes and sodium chloride (1.73 g) was added thereto. Thereafter, the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in chlorobenzene. The previously prepared isophthalimide solution and 15% hydrogen peroxide (4.9 g) were alternately and slowly dropped into a mixture of 2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]aniline (5.15 g), p-toluenesulfonic acid monohydrate (0.09 g) and chlorobenzene (3 mL) at 50° C. and then stirred at 60° C. for 3 hours. An aqueous sodium sulfite solution was added dropwise to the thus obtained reaction mixture at the same temperature to decompose the excess oxidizing agent. After neutralization with an aqueous sodium hydrogencarbonate solution, the resulting mixture was slowly cooled to 20° C. The crystals precipitated were filtered, washed with water and then dried to obtain 9.06 g (yield 85%) of the title compound. by adding After completion of the dropwise addition Thereafter, the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in chlorobenzene stirred at 60° C. for 3 hours The crystals precipitated were filtered washed with water dried

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Phthaloyl dichloride (18.78 g) was added dropwise to a mixture of aqueous sodium hydroxide solution (7.59 g/55 mL), 2-methyl-1-methylthio-2-propanamine (11.03 g) and 1,2-dichloroethane (55 mL) at 40° C. or lower. After completion of the dropwise addition, the resulting mixture was stirred at 40° C. for 30 minutes and the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane. The previously prepared isophthalimide solution and 35% hydrogen peroxide (9.89 g) were slowly dropped at the same time into a mixture of 2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]aniline (24.18 g), p-toluenesulfonic acid monohydrate (0.44 g) and 1,2-dichloroethane (13.75 mL) at 60° C. and then stirred at 60° C. for 1 hour. An aqueous sodium sulfite solution was added dropwise to the thus obtained reaction mixture at the same temperature to decompose the excess oxidizing agent. Then, the resulting mixture was neutralized with an aqueous sodium hydrogencarbonate solution, after which the organic layer was separated. The organic layer obtained was slowly cooled to 20° C. The crystals precipitated were filtered, washed with water and then dried to obtain 41.70 g (yield 83%) of the title compound. After completion of the dropwise addition the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane stirred at 60° C. for 1 hour after which the organic layer was separated The organic layer obtained was slowly cooled to 20° C The crystals precipitated were filtered washed with water dried

反应条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Phthaloyl dichloride (100.0 g) was added dropwise to a mixture of aqueous sodium hydroxide solution (40.39 g/300 mL), 2-methyl-1-methylthio-2-propanamine (61.66 g) and chloroform (300 mL) at 25° C. or lower. After completion of the dropwise addition, the resulting mixture was stirred at 20° C. for 30 minutes and the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane. The previously prepared isophthalimide solution was added dropwise to a mixture of 2,3,4-trichloroaniline (91.93 g), p-toluenesulfonic acid monohydrate (2.34 g) and chloroform (75 mL) at 60° C. and then stirred for 30 minutes. Subsequently, formic acid (2.27 g) was added thereto and then 35% hydrogen peroxide (52.66 g) was slowly dropped thereinto with heating under reflux. Thereafter, the resulting mixture was stirred at 60° C. for 3 hours. An aqueous sodium sulfite solution was added dropwise to the thus obtained reaction mixture at the same temperature to decompose the excess oxidizing agent. Then, the resulting mixture was neutralized with an aqueous sodium hydrogencarbonate solution, after which the organic layer was separated. The organic layer obtained was heated at 60° C. Heptane (800 mL) was added dropwise thereto and the resulting mixture was slowly cooled to 20° C. The crystals precipitated were filtered, washed with water and then dried to obtain 202.44 g (yield 89%) of the title compound. After completion of the dropwise addition the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane stirred for 30 minutes with heating under reflux Thereafter, the resulting mixture was stirred at 60° C. for 3 hours after which the organic layer was separated The organic layer obtained was heated at 60° C the resulting mixture was slowly cooled to 20° C The crystals precipitated were filtered washed with water dried

反应条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-methyl-1-methylthio-2-propanamine (11.61 g) and triethylamine (1.97 g) was added dropwise to a mixture of phthalic anhydride (14.42 g) and 1,2-dichloroethane (58 mL) at 50° C. The resulting mixture was stirred at the same temperature for 30 minutes to prepare N-[1,1-dimethyl-2-(methylthio)ethyl]phthalamic acid. Aqueous sodium hydrogencarbonate solution (9.81 g/101 mL) was added dropwise to this mixture at 40° C. and then methyl chloroformate (11.04 g) was added dropwise thereto at the same temperature. After completion of the dropwise addition, the reaction mixture was stirred at 50° C. for 1 hour and the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane. This solution was added dropwise to a mixture of 2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoro-methyl)ethyl]aniline (25.45 g), concentrated hydrochloric acid (0.49 g) and 1,2-dichloroethane (14.4 mL) at 60° C., and then stirred at 65° C. for 30 minutes to prepare a solution of N2-[1,1-dimethyl-2-(methylthio)ethyl]-N1-{2-methyl-4-{1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl}phenyl}-1,2-benzenedicarboxamide in 1,2-dichloroethane. Formic acid (0.94 g) was added to this solution, followed by adding dropwise thereto 35% hydrogen peroxide (10.41 g) at 60° C. After completion of the dropwise addition, the resulting mixture was stirred at 60° C. for 1 hour and an aqueous sodium sulfite solution was added dropwise to the thus obtained reaction mixture at the same temperature to decompose the excess oxidizing agent. Then, the resulting mixture was neutralized with an aqueous sodium hydrogencarbonate solution, after which the organic layer was separated. The organic layer obtained was slowly cooled to 20° C. The crystals precipitated were filtered, washed with water and then dried to obtain 43.89 g (yield 83%) of the title compound. After completion of the dropwise addition the reaction mixture was stirred at 50° C. for 1 hour the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane stirred at 65° C. for 30 minutes by adding dropwise at 60° C After completion of the dropwise addition the resulting mixture was stirred at 60° C. for 1 hour after which the organic layer was separated The organic layer obtained The crystals precipitated were filtered washed with water dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-methyl-1-methylthio-2-propanamine (11.61 g) and triethylamine (1.97 g) was added dropwise to a mixture of phthalic anhydride (14.42 g) and 1,2-dichloroethane (58 mL) at 50° C. The resulting mixture was stirred at the same temperature for 30 minutes to prepare N-[1,1-dimethyl-2-(methylthio)ethyl]phthalamic acid. Aqueous sodium hydrogencarbonate solution (9.81 g/101 mL) was added dropwise to this mixture at 40° C. and then methyl chloroformate (11.04 g) was added dropwise thereto at the same temperature. After completion of the dropwise addition, the reaction mixture was stirred at 50° C. for 1 hour and the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane. This solution was added dropwise to a mixture of 2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoro-methyl)ethyl]aniline (25.45 g), concentrated hydrochloric acid (0.49 g) and 1,2-dichloroethane (14.4 mL) at 60° C., and then stirred at 65° C. for 30 minutes. The reaction mixture was cooled and then neutralized with an aqueous sodium hydrogencarbonate solution, after which the organic layer was separated. The organic layer obtained was concentrated under reduced pressure, and the crystals precipitated were filtered, washed with water and then dried to obtain 47.06 g (yield 92%) of the title compound. After completion of the dropwise addition the reaction mixture was stirred at 50° C. for 1 hour the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane stirred at 65° C. for 30 minutes The reaction mixture was cooled after which the organic layer was separated The organic layer obtained was concentrated under reduced pressure the crystals precipitated were filtered washed with water dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-methyl-1-methylthio-2-propanamine (11.61 g) and triethylamine (1.97 g) was added dropwise to a mixture of phthalic anhydride (14.42 g) and 1,2-dichloroethane (58 mL) at 50° C. The resulting mixture was stirred at the same temperature for 30 minutes to prepare N-[1,1-dimethyl-2-(methylthio)ethyl]phthalamic acid. Aqueous sodium hydrogencarbonate solution (9.81 g/101 mL) was added dropwise to this mixture at 40° C. and then methyl chloroformate (11.04 g) was added dropwise thereto at the same temperature. After completion of the dropwise addition, the reaction mixture was stirred at 50° C. for 1 hour and the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane. This solution was added dropwise to a mixture of 2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoro-methyl)ethyl]aniline (25.45 g), concentrated hydrochloric acid (0.49 g) and 1,2-dichloroethane (14.4 mL) at 60° C., and then stirred at 65° C. for 30 minutes. The reaction mixture was cooled and then neutralized with an aqueous sodium hydrogencarbonate solution, after which the organic layer was separated. The organic layer obtained was concentrated under reduced pressure, and the crystals precipitated were filtered, washed with water and then dried to obtain 47.06 g (yield 92%) of the title compound. After completion of the dropwise addition the reaction mixture was stirred at 50° C. for 1 hour the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane stirred at 65° C. for 30 minutes The reaction mixture was cooled after which the organic layer was separated The organic layer obtained was concentrated under reduced pressure the crystals precipitated were filtered washed with water dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-methyl-1-methylthio-2-propanamine (11.61 g) and triethylamine (1.97 g) was added dropwise to a mixture of phthalic anhydride (14.42 g) and 1,2-dichloroethane (58 mL) at 50° C. The resulting mixture was stirred at the same temperature for 30 minutes to prepare N-[1,1-dimethyl-2-(methylthio)ethyl]phthalamic acid. Aqueous sodium hydrogencarbonate solution (9.81 g/101 mL) was added dropwise to this mixture at 40° C. and then methyl chloroformate (11.04 g) was added dropwise thereto at the same temperature. After completion of the dropwise addition, the reaction mixture was stirred at 50° C. for 1 hour and the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane. This solution was added dropwise to a mixture of 2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoro-methyl)ethyl]aniline (25.45 g), concentrated hydrochloric acid (0.49 g) and 1,2-dichloroethane (14.4 mL) at 60° C., and then stirred at 65° C. for 30 minutes. The reaction mixture was cooled and then neutralized with an aqueous sodium hydrogencarbonate solution, after which the organic layer was separated. The organic layer obtained was concentrated under reduced pressure, and the crystals precipitated were filtered, washed with water and then dried to obtain 47.06 g (yield 92%) of the title compound. After completion of the dropwise addition the reaction mixture was stirred at 50° C. for 1 hour the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane stirred at 65° C. for 30 minutes The reaction mixture was cooled after which the organic layer was separated The organic layer obtained was concentrated under reduced pressure the crystals precipitated were filtered washed with water dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In tetrahydrofuran (300 ml) was dissolved 23.86 g (200 mmol) of 1,1-dimethyl-2-(methylthio)ethylamine, and 103.4 g (200 mmol) of a 30% solution of carbobenzoxy chloride in toluene and then a solution of 24.29 g (240 mmol) of triethylamine in tetrahydrofuran were slowly dropped thereinto under ice-cooling. After the resulting mixture was stirred at room temperature for 3 hours, the triethylamine hydrochloride precipitated was filtered under reduced pressure and washed with ethyl acetate. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to obtain 36.35 g (yield 72%) of benzyl 1,1-dimethyl-2-(methylthio)ethylcarbamate. under ice-cooling the triethylamine hydrochloride precipitated was filtered under reduced pressure washed with ethyl acetate The filtrate was concentrated under reduced pressure the residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)