ethanethioic S-acid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (2S,4R)-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)-2-[2-(4-nitrobenzyloxycarbonylamino)ethyloxymethyl]pyrrolidine (0.90 g) in dimethylformamide (2 ml) was added to a reaction mixture of thioacetic S-acid (0.16 ml) and sodium hydride (62.8% in oil suspension) (0.07 g) in dimethylformamide (9 ml) in a nitrogen stream and the mixture was heated at 70°-75° C. for 6 hours. The mixture was poured into water (100 ml), extracted with ethyl acetate (50 ml×2), dried over magnesium sulfate and concentrated under reduced pressure to give a syrup. The syrup was subjected to a column chromatography on silica gel (20 g) and eluted with chloroform to give (2S,4S)-4-acetylthio-1-(4-nitrobenzyloxycarbonyl)-2-[2-(4-nitrobenzyloxycarbonylamino)ethyloxymethyl]pyrrolidine (0.60 g). the mixture was heated at 70°-75° C. for 6 hours extracted with ethyl acetate (50 ml×2) dried over magnesium sulfate concentrated under reduced pressure to give a syrup eluted with chloroform

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (2S,4R)-2-(carbamoylmethyl)oxymethyl-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (0.98 g) in dimethylformamide (2 ml) was added to a reaction mixture of thioacetic S-acid (0.25 ml) and sodium hydride (62.8% in oil suspension) (0.11 g) in dimethylformamide (10 ml) in a nitrogen stream and the mixture was heated at 70°-75° C. for 3 hours. The mixture was poured into water (100 ml), extracted with ethyl acetate (50 ml×3), dried over magnesium sulfate and concentrated under reduced pressure to give a syrup. The syrup was subjected to a column chromatography on silica gel (20 g) and eluted with a mixture of methanol and chloroform (1:99 v/v) to give (2S,4S)-4-acetylthio-2-(carbamoylmethyl)oxymethyl-1-(4nitrobenzyloxycarbonyl)pyrrolidine (0.72 g). the mixture was heated at 70°-75° C. for 3 hours extracted with ethyl acetate (50 ml×3) dried over magnesium sulfate concentrated under reduced pressure to give a syrup eluted with a mixture of methanol and chloroform (1:99 v/v)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (2S,4R)-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)-2-[2-(4-nitrobenzyloxycarbonylamino)ethyloxymethyl]pyrrolidine (0.90 g) in dimethylformamide (2 ml) was added to a reaction mixture of thioacetic S-acid (0.16 ml) and sodium hydride (62.8% in oil suspension) (0.07 g) in dimethylformamide (9 ml) in a nitrogen stream and the mixture was heated at 70°-75° C. for 6 hours. The mixture was poured into water (100 ml), extracted with ethyl acetate (50 ml×2), dried over magnesium sulfate and concentrated under reduced pressure to give a syrup. The syrup was subjected to a column chromatography on silica gel (20 g) and eluted with chloroform to give (2S,4S)-4-acetylthio-1-(4-nitrobenzyloxycarbonyl)-2-[2-(4-nitrobenzyloxycarbonylamino)ethyloxymethyl]pyrrolidine (0.60 g). the mixture was heated at 70°-75° C. for 6 hours extracted with ethyl acetate (50 ml×2) dried over magnesium sulfate concentrated under reduced pressure to give a syrup eluted with chloroform

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (2S,4R)-2-(carbamoylmethyl)oxymethyl-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (0.98 g) in dimethylformamide (2 ml) was added to a reaction mixture of thioacetic S-acid (0.25 ml) and sodium hydride (62.8% in oil suspension) (0.11 g) in dimethylformamide (10 ml) in a nitrogen stream and the mixture was heated at 70°-75° C. for 3 hours. The mixture was poured into water (100 ml), extracted with ethyl acetate (50 ml×3), dried over magnesium sulfate and concentrated under reduced pressure to give a syrup. The syrup was subjected to a column chromatography on silica gel (20 g) and eluted with a mixture of methanol and chloroform (1:99 v/v) to give (2S,4S)-4-acetylthio-2-(carbamoylmethyl)oxymethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (0.72 g). the mixture was heated at 70°-75° C. for 3 hours extracted with ethyl acetate (50 ml×3) dried over magnesium sulfate concentrated under reduced pressure to give a syrup eluted with a mixture of methanol and chloroform (1:99 v/v)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (2S,4R)-2-(carbamoylmethyl)oxymethyl-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (0.98 g) in dimethylformamide (2 ml) was added to a reaction mixture of thioacetic S-acid (0.25 ml) and sodium hydride (62.8% in oil suspension) (0.11 g) in dimethylformamide (10 ml) in a nitrogen stream and the mixture was heated at 70°-75° C. for 3 hours. The mixture was poured into water (100 ml), extracted with ethyl acetate (50 ml×3), dried over magnesium sulfate and concentrated under reduced pressure to give a syrup. The syrup was subjected to a column chromatography on silica gel (20 g) and eluted with a mixture of methanol and chloroform (1:99 v/v) to give (2S,4S)-4-acetylthio-2-(carbamoylmethyl)oxymethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (0.72 g). the mixture was heated at 70°-75° C. for 3 hours extracted with ethyl acetate (50 ml×3) dried over magnesium sulfate concentrated under reduced pressure to give a syrup eluted with a mixture of methanol and chloroform (1:99 v/v)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of calcium hydroxide (2.25 g) and (2S,4R)-1-allyloxycarbonyl-2-(imidazol-1-yl)methyl-4-methanesulfonyloxypyrrolidine (10 g) in 4-methyl-2-pentanone (60 ml) was added dropwise thioacetic S-acid (4.38 ml) with stirring below 45° C. The solvent (18 ml) of the mixture was removed under reduced pressure at 40°-45° C. The resulting suspension was heated at 80°-85° C. for 2 hours. After cooling, water (20 ml) and ethyl acetate (20 ml) was added to the reaction mixture The insoluble material was filtered off and washed with ethyl acetate (30 ml). The filtrate and washing were combined. The organic layer was washed with saturated aqueous sodium chloride, dried over magnesium sulfate and evaporated in vacuo to give (2S,4S)-4-acetylthio-1-allyloxycarbonyl-2-(imidazol-1-yl)methylpyrrolidine (7.94 g). The solvent (18 ml) of the mixture was removed under reduced pressure at 40°-45° C The resulting suspension was heated at 80°-85° C. for 2 hours After cooling water (20 ml) and ethyl acetate (20 ml) was added to the reaction mixture The insoluble material was filtered off washed with ethyl acetate (30 ml) The filtrate and washing The organic layer was washed with saturated aqueous sodium chloride dried over magnesium sulfate evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (2S,4R)-2-(imidazol-1-yl)methyl-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (0.76 g) in dimethylformamide (2 ml) was added to a mixture of thioacetic S-acid (0.16 ml) and sodium hydride (62.8 % in oil suspension, 0.08 g) in dimethylformamide (5 ml) under nitrogen stream and the mixture was heated at 70°-75° C. for 5 hours. The mixture was poured into ice-water (70 ml), extracted with ethyl acetate (70 ml), dried over magnesium sulfate and concentrated under reduced pressure to give a syrup. The syrup was subjected to a column chromatography on silica gel (20 g) and eluted with a mixture of methanol and chloroform (2:98, V/V) to give (2S,4S)-4-acetylthio-2-(imidazol-1-yl)methyl-1-(-4-nitrobenzyloxycarbonyl)pyrrolidine (0.38 g). the mixture was heated at 70°-75° C. for 5 hours extracted with ethyl acetate (70 ml) dried over magnesium sulfate concentrated under reduced pressure to give a syrup eluted with a mixture of methanol and chloroform (2:98, V/V)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2R,4R)-1-Allyloxycarbonyl-2-[2-(2-hydroxymethyl-imidazol-1-yl) ethyl]-4-methanesulfonyloxypyrrolidine (15.7 g) was reacted with thioacetic S-acid (6.30 ml) in substantially the same manner as that of Preparation 4-12) to give (2R,4S)-4-acetylthio-1-allyloxycarbonyl-2-[2-(2-hydroxymethylimidazol-1-yl) ethyl]pyrrolidine (5.93 g) as an orange paste. of Preparation 4-12)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2S,4R)-4-Hydroxy-1-(4-nitrobenzyloxycarbonyl)-2-[1-(4-nitrobenzyloxycarbonyl)-2-imidazolin-2-yl]pyrrolidine (655 mg) and triphenylphosphine (0.51 g) were dissolved in tetrahydrofuran (20 ml) at 0° C. To this solution was added dropwise a solution of diethyl azodicarboxylate (0.30 ml) in tetrahydrofuran (5 ml) with stirring for 30 minutes, followed by addition of a solution of thioacetic S-acid (0.14 ml). Stirring was continued at ambient temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate and brine, dried over magnesium sulfate and evaporated. The obtained oily residue was subjected to a column chromatography on silica gel and eluted with a mixture of dichloromethane and acetone (20:1, V/V) to give (2S,4S)-4-acetylthio-1-(4-nitrobenzyloxycarbonyl)-2-[1-(4-nitrobenzyloxycarbonyl)-2-imidazolin-2-yl]pyrrolidine (1.2 g). Stirring was continued at ambient temperature for 2 hours washed with saturated sodium bicarbonate and brine dried over magnesium sulfate evaporated eluted with a mixture of dichloromethane and acetone (20:1, V/V)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2S,4R)-4-Hydroxy-1-(4-nitrobenzyloxycarbonyl)-2-[1-(4-nitrobenzyloxycarbonyl)-2-imidazolin-2-yl]pyrrolidine (655 mg) and triphenylphosphine (0.51 g) were dissolved in tetrahydrofuran (20 ml) at 0° C. To this solution was added dropwise a solution of diethyl azodicarboxylate (0.30 ml) in tetrahydrofuran (5 ml) with stirring for 30 minutes, followed by addition of a solution of thioacetic S-acid (0.14 ml). Stirring was continued at ambient temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate and brine, dried over magnesium sulfate and evaporated. The obtained oily residue was subjected to a column chromatography on silica gel and eluted with a mixture of dichloromethane and acetone (20:1, V/V) to give (2S,4S)-4-acetylthio-1-(4-nitrobenzyloxycarbonyl)-2-[1-(4-nitrobenzyloxycarbonyl)-2-imidazolin-2-yl]pyrrolidine (1.2 g). Stirring was continued at ambient temperature for 2 hours washed with saturated sodium bicarbonate and brine dried over magnesium sulfate evaporated eluted with a mixture of dichloromethane and acetone (20:1, V/V)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of sodium hydride (62.8% dispersion in mineral oil, 285 mg) in N,N-dimethylformamide (30 ml) was added thioacetic S-acid (0.54 ml) at 0°-5° C. under an atmosphere of nitrogen. After evolution of hydrogen ceased, the mixture was stirred at room temperature, and (2S,4R)-2-(2-aminothiazol-4-yl)-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.6 g) in N,N-dimethylformamide (20 ml) was added thereto. The mixture was stirred at 90° C. for 5 hours and poured into a mixture of ethyl acetate (100 ml) and water (100 ml). The aqueous layer was separated and extracted twice with ethyl acetate (50 ml). The organic layers were combined, washed with brine, dried over magnesium sulfate and concentrated under reduced pressure to give a syrup. The syrup was subjected to a column chromatography on silica gel (60 g) eluting with a mixture of acetone and dichloromethane (1:5 V/V) to give (2S,4S)-4-acetylthio-2-(2-aminothiazol-4-yl)-1 -(4-nitrobenzyloxycarbonyl)pyrrolidine (1.26 g). The mixture was stirred at 90° C. for 5 hours The aqueous layer was separated extracted twice with ethyl acetate (50 ml) washed with brine dried over magnesium sulfate concentrated under reduced pressure to give a syrup eluting with a mixture of acetone and dichloromethane (1:5 V/V)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of sodium hydride (62.8% dispersion in mineral oil, 285 mg) in N,N-dimethylformamide (30 ml) was added thioacetic S-acid (0.54 ml) at 0°-5° C. under an atmosphere of nitrogen. After evolution of hydrogen ceased, the mixture was stirred at room temperature, and (2S,4R)-2-(2-aminothiazol-4-yl)-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.6 g) in N,N-dimethylformamide (20 ml) was added thereto. The mixture was stirred at 90° C. for 5 hours and poured into a mixture of ethyl acetate (100 ml) and water (100 ml). The aqueous layer was separated and extracted twice with ethyl acetate (50 ml). The organic layers were combined, washed with brine, dried over magnesium sulfate and concentrated under reduced pressure to give a syrup. The syrup was subjected to a column chromatography on silica gel (60 g) eluting with a mixture of acetone and dichloromethane (1:5 V/V) to give (2S,4S)-4-acetylthio-2-(2-aminothiazol-4-yl)-1 -(4-nitrobenzyloxycarbonyl)pyrrolidine (1.26 g). The mixture was stirred at 90° C. for 5 hours The aqueous layer was separated extracted twice with ethyl acetate (50 ml) washed with brine dried over magnesium sulfate concentrated under reduced pressure to give a syrup eluting with a mixture of acetone and dichloromethane (1:5 V/V)