benzenecarbothioic S-acid

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

実験手順: To a solution of (2S,4R)-4-hydroxy-2-(1-methyl-1H-tetrazol-5-yl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.23 g) and triphenylphosphine (1.23 g) in tetrahydrofuran (25 ml) was added dropwise a solution of diethyl azodicarboxylate (0.74 ml) in tetrahydrofuran (2 ml) under ice-cooling. After stirring at the same temperature for 30 minutes, to the solution was added thiobenzoic S-acid (0.55 ml) under ice-cooling. The mixture was stirred at the same temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was dissolved in ethyl acetate (100 ml) and the solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (19:1, V/V). The fractions containing the resired compound were collected and evaporated in vacuo to give (2S,4S)-4-benzoylthio-2-(1-methyl-1H-tetrazol- 5-yl)thiomethyl-1(4-nitrobenzyloxycarbonyl)pyrrolidine (1.61 g). cooling cooling The mixture was stirred at the same temperature for 2 hours The reaction mixture was concentrated under reduced pressure to give a residue the solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively dried over anhydrous magnesium sulfate evaporated in vacuo The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (19:1, V/V) The fractions containing the resired compound were collected evaporated in vacuo

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

実験手順: To a suspension of sodium hydride (62.8% in oil) (0.22 g) in N,N-dimethylformamide (5 ml) was added dropwise thiobenzoic S-acid (0.66 ml) under ice-cooling. After stirring under the same condition for 30 minutes, this solution was added to a solution of (2S,4R)-2-(carbamoylmethyl)thiomethyl-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.68 g) in N,N-dimethylformamide (20 ml) at ambient temperature. The mixture was stirred at 70°-80° C. for 1 hour. The reaction mixture was poured into ice-water (50 ml) and extracted twice with ethyl acetate (50 ml). The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and evaporated in vacuo t.o give a residue. The residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (5:1, V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4S)-4-benzoylthio-2-(carbamoylmethyl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (0.87 g). cooling The mixture was stirred at 70°-80° C. for 1 hour extracted twice with ethyl acetate (50 ml) The organic layer was washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate evaporated in vacuo t.o give a residue The residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (5:1, V/V) The fractions containing the desired compound were collected evaporated in vacuo

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

実験手順: To a solution of (2S,4R)-2-(difluoromethyl)thiomethyl-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.01 g) and triphenylphosphine (1.1 g) in tetrahydrofuran (20 ml) was added dropwise a solution of diethyl azodicarboxylate (0.66 ml) in tetrahydrofuran (3 ml) at -10° C. to -5° C. with stirring. The mixture was stirred at the same temperature for 30 minutes. To the solution was added thiobenzoic S-acid (0.49 ml) at the same temperature and the mixture was stirred under ice-cooling for 2 hours. The reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (60 ml). The solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of n-hexane and ethyl acetate (3.1 , V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4S)-4-benzoylthio-2-(difluoromethyl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.01 g). The mixture was stirred at the same temperature for 30 minutes the mixture was stirred under ice- cooling for 2 hours The reaction mixture was concentrated under reduced pressure The resulting residue was dissolved in ethyl acetate (60 ml) The solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively dried over anhydrous magnesium sulfate evaporated in vacuo The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of n-hexane and ethyl acetate (3.1 , V/V) The fractions containing the desired compound were collected evaporated in vacuo

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

実験手順: To a solution of (2S,4R)-4-hydroxy-2-(1-methyl-1H-tetrazol-5-yl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.23 g) and triphenylphosphine (1.23 g) in tetrahydrofuran (25 ml) was added dropwise a solution of diethyl azodicarboxylate (0.74 ml) in tetrahydrofuran (2 ml) under ice-cooling. After stirring at the same temperature for 30 minutes, to the solution was added thiobenzoic S-acid (0.55 ml) under ice-cooling. The mixture was stirred at the same temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was dissolved in ethyl acetate (100 ml) and the solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (19:1, V/V). The fractions containing the resired compound were collected and evaporated in vacuo to give (2S,4S)-4-benzoylthio-2-(1-methyl-1H-tetrazol- 5-yl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.61 g). cooling cooling The mixture was stirred at the same temperature for 2 hours The reaction mixture was concentrated under reduced pressure to give a residue the solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively dried over anhydrous magnesium sulfate evaporated in vacuo The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (19:1, V/V) The fractions containing the resired compound were collected evaporated in vacuo

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

実験手順: To a suspension of sodium hydride (62.8% in oil) (0.22 g) in N,N-dimethylformamide (5 ml) was added dropwise thiobenzoic S-acid (0.66 ml) under ice-cooling. After stirring under the same condition for 30 minutes, this solution was added to a solution of (2S,4R)-2-(carbamoylmethyl)thiomethyl-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.68 g) in N,N-dimethylformamide (20 ml) at ambient temperature. The mixture was stirred at 70°-80° C. for 1 hour. The reaction mixture was poured into ice-water (50 ml) and extracted twice with ethyl acetate (50 ml). The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and evaporated in vacuo to give a residue. The residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (5:1, V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4S)-4-benzoylthio-2-(carbamoylmethyl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (0.87 g). cooling The mixture was stirred at 70°-80° C. for 1 hour extracted twice with ethyl acetate (50 ml) The organic layer was washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate evaporated in vacuo to give a residue The residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (5:1, V/V) The fractions containing the desired compound were collected evaporated in vacuo

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

実験手順: To a solution of (2S,4R)-2-(difluoromethyl)thiomethyl-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.01 g) and triphenylphosphine (1.1 g) in tetrahydrofuran (20 ml) was added dropwise a solution of diethyl azodicarboxylate (0.66 ml) in tetrahydrofuran (3 ml) at -10° C. to -5° C. with stirring. The mixture was stirred at the same temperature for 30 minutes. To the solution was added thiobenzoic S-acid (0.49 ml) at the same temperature and the mixture was stirred under ice-cooling for 2 hours. The reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (60 ml). The solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of n-hexane and ethyl acetate (3:1, V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4S)-4-benzoylthio-2-(difluoromethyl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.01 g). The mixture was stirred at the same temperature for 30 minutes the mixture was stirred under ice- cooling for 2 hours The reaction mixture was concentrated under reduced pressure The resulting residue was dissolved in ethyl acetate (60 ml) The solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively dried over anhydrous magnesium sulfate evaporated in vacuo The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of n-hexane and ethyl acetate (3:1, V/V) The fractions containing the desired compound were collected evaporated in vacuo

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

実験手順: To a solution of potassium t-butoxide (8.42 g) in dimethylformamide (70 ml) was added thiobenzoic S-acid (9.27 ml) dropwise at -20° C. under dry ice--acetone bath. After the addition, the solution was warmed to room temperature, and then stirred for 75 minutes. To the solution was added a solution of (2R,4R)-1-allyloxycarbonyl-2-[2-(2-carbamoylimidazol-1-yl)ethyl]-4-methylsulfonyloxypyrrolidine (14.5 g) in dimethylformamide (70 ml) and the mixture was heated to 85° C. and stirred for 2 hours. After cooling to room temperature, the mixture was quenched by the addition of water (280 ml) and extracted with ethyl acetate (140 ml×3). The combined extract was washed with aqueous saturated sodium bicarbonate solution (140 ml×2), water (200 ml×2), and brine (200 ml×2), and then dried over magnesium sulfate. The solvent was evaporated and the residue was chromatographed on a 150 g of silica gel eluting with a mixture of chloroform and methanol (95:5, V/V) to give (2R,4S)-1-allyloxycarbonyl-4-benzoylthio-2-[2-(2-carbamoylimidazol-1-yl) ethyl]pyrrolidine (11.2 g) as a yellow paste. After the addition the mixture was heated to 85° C. stirred for 2 hours After cooling to room temperature the mixture was quenched by the addition of water (280 ml) extracted with ethyl acetate (140 ml×3) The combined extract was washed with aqueous saturated sodium bicarbonate solution (140 ml×2), water (200 ml×2), and brine (200 ml×2) dried over magnesium sulfate The solvent was evaporated the residue was chromatographed on a 150 g of silica gel eluting with a mixture of chloroform and methanol (95:5, V/V)

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

実験手順: To a solution of potassium t-butoxide (8.42 g) in dimethylformamide (70 ml) was added thiobenzoic S-acid (9.27 ml) dropwise at -20° C. under dry ice--acetone bath. After the addition, the solution was warmed to room temperature, and then stirred for 75 minutes. To the solution was added a solution of (2R,4R)-1-allyloxycarbonyl-2-[2-(2-carbamoylimidazol-1-yl)ethyl]-4-methylsulfonyloxypyrrolidine (14.5 g) in dimethylformamide (70 ml) and the mixture was heated to 85° C. and stirred for 2 hours. After cooling to room temperature, the mixture was quenched by the addition of water (280 ml) and extracted with ethyl acetate (140 ml×3). The combined extract was washed with aqueous saturated sodium bicarbonate solution (140 ml×2), water (200 ml×2), and brine (200 ml×2), and then dried over magnesium sulfate. The solvent was evaporated and the residue was chromatographed on a 150 g of silica gel eluting with a mixture of chloroform and methanol (95:5, V/V) to give (2R,4S)-1-allyloxycarbonyl-4-benzoylthio-2-[2-(2-carbamoylimidazol-1-yl) ethyl]pyrrolidine (11.2 g) as a yellow paste. After the addition the mixture was heated to 85° C. stirred for 2 hours After cooling to room temperature the mixture was quenched by the addition of water (280 ml) extracted with ethyl acetate (140 ml×3) The combined extract was washed with aqueous saturated sodium bicarbonate solution (140 ml×2), water (200 ml×2), and brine (200 ml×2) dried over magnesium sulfate The solvent was evaporated the residue was chromatographed on a 150 g of silica gel eluting with a mixture of chloroform and methanol (95:5, V/V)

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

実験手順: To a solution of (2S,4R)-4-hydroxy-2-(1-methyl-1H-tetrazol-5-yl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.23 g) and triphenylphosphine (1.23 g) in tetrahydrofuran (25 ml) was added dropwise a solution of diethyl azodicarboxylate (0.74 ml) in tetrahydrofuran (2 ml) under ice-cooling. After stirring at the same temperature for 30 minutes, to the solution was added thiobenzoic S-acid (0.55 ml) under ice-cooling. The mixture was stirred at the same temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was dissolved in ethyl acetate (100 ml) and the solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (19:1, V/V). The fractions containing the resired compound were collected and evaporated in vacuo to give (2S,4S)-4-benzoylthio-2-(1-methyl-1H-tetrazol- 5-yl)thiomethyl-1(4-nitrobenzyloxycarbonyl)pyrrolidine (1.61 g). cooling cooling The mixture was stirred at the same temperature for 2 hours The reaction mixture was concentrated under reduced pressure to give a residue the solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively dried over anhydrous magnesium sulfate evaporated in vacuo The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (19:1, V/V) The fractions containing the resired compound were collected evaporated in vacuo

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

実験手順: To a solution of (2S,4R)-4-hydroxy-2-(1-methyl-1H-tetrazol-5-yl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.23 g) and triphenylphosphine (1.23 g) in tetrahydrofuran (25 ml) was added dropwise a solution of diethyl azodicarboxylate (0.74 ml) in tetrahydrofuran (2 ml) under ice-cooling. After stirring at the same temperature for 30 minutes, to the solution was added thiobenzoic S-acid (0.55 ml) under ice-cooling. The mixture was stirred at the same temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was dissolved in ethyl acetate (100 ml) and the solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (19:1, V/V). The fractions containing the resired compound were collected and evaporated in vacuo to give (2S,4S)-4-benzoylthio-2-(1-methyl-1H-tetrazol- 5-yl)thiomethyl-1(4-nitrobenzyloxycarbonyl)pyrrolidine (1.61 g). cooling cooling The mixture was stirred at the same temperature for 2 hours The reaction mixture was concentrated under reduced pressure to give a residue the solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively dried over anhydrous magnesium sulfate evaporated in vacuo The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (19:1, V/V) The fractions containing the resired compound were collected evaporated in vacuo

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

実験手順: To a suspension of sodium hydride (62.8% in oil) (0.22 g) in N,N-dimethylformamide (5 ml) was added dropwise thiobenzoic S-acid (0.66 ml) under ice-cooling. After stirring under the same condition for 30 minutes, this solution was added to a solution of (2S,4R)-2-(carbamoylmethyl)thiomethyl-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.68 g) in N,N-dimethylformamide (20 ml) at ambient temperature. The mixture was stirred at 70°-80° C. for 1 hour. The reaction mixture was poured into ice-water (50 ml) and extracted twice with ethyl acetate (50 ml). The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and evaporated in vacuo t.o give a residue. The residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (5:1, V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4S)-4-benzoylthio-2-(carbamoylmethyl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (0.87 g). cooling The mixture was stirred at 70°-80° C. for 1 hour extracted twice with ethyl acetate (50 ml) The organic layer was washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate evaporated in vacuo t.o give a residue The residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (5:1, V/V) The fractions containing the desired compound were collected evaporated in vacuo

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

実験手順: To a solution of (2S,4R)-2-(difluoromethyl)thiomethyl-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.01 g) and triphenylphosphine (1.1 g) in tetrahydrofuran (20 ml) was added dropwise a solution of diethyl azodicarboxylate (0.66 ml) in tetrahydrofuran (3 ml) at -10° C. to -5° C. with stirring. The mixture was stirred at the same temperature for 30 minutes. To the solution was added thiobenzoic S-acid (0.49 ml) at the same temperature and the mixture was stirred under ice-cooling for 2 hours. The reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (60 ml). The solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of n-hexane and ethyl acetate (3.1 , V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4S)-4-benzoylthio-2-(difluoromethyl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.01 g). The mixture was stirred at the same temperature for 30 minutes the mixture was stirred under ice- cooling for 2 hours The reaction mixture was concentrated under reduced pressure The resulting residue was dissolved in ethyl acetate (60 ml) The solution was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively dried over anhydrous magnesium sulfate evaporated in vacuo The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of n-hexane and ethyl acetate (3.1 , V/V) The fractions containing the desired compound were collected evaporated in vacuo