prop-2-enyl N-sulfamoylcarbamate

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

Procedure: To a solution of (2S,4S)-4-acetylthio-1-allyloxycarbonylpyrrolidine-2-methanol (8.02 g: ca. 30 mmole) in ethyl acetate (83 ml) under ice cooling, triphenylphosphine (9.44 g: 13.6 mmole), N-allyloxycarbonylsulfamide (3.12 g: 15.9 mmole), and azodicarboxylic acid diethylester (5.67 ml: 36 mmole) are successively added. The mixture is stirred under ice cooling for 55 minutes and at room temperature for 4 hours. The reaction mixture is dissolved in toluene (60 ml), concentrated, diluted with toluene (60 ml), filtered to remove separating crystals, and the filtrate is concentrated. The residue is purified by silica gel chromatography to give (2S,4S)-4-acetylthio-1-allyloxycarbonyl-2-(N-sulfamoyl-N-allyloxycarbonylamino)methylpyrrolidine (6.74 g). Yield: 55%. Colorless oil. NMR δ(CDCl3) ppm: 1.5 to 1.7(m, 1H), 2.35(s, 3H), 2.5 to 2.7(m, 1H), 3.19 (dd, J=6.3 Hz, J=11.5 Hz, 1H), 3.68 (dd, J=3.8 Hz, J=14.5 Hz, 1H), 3.9 to 4.3(m, 3H), 4.3 to 4.7(m, 5H), 5.2 to 5.4(m, 4H), 5.8 to 6.1(m, 4H). concentrated diluted with toluene (60 ml) filtered to remove separating crystals the filtrate is concentrated The residue is purified by silica gel chromatography

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

Procedure: To a solution of (2S,4S)-4-acetylthio-1-allyloxycarbonylpyrrolidine-2-methanol (8.02 g: ca. 30 mmole) in ethyl acetate (83 ml) under ice cooling, triphenylphosphine (9.44 g: 13.6 mmole), N-allyloxycarbonylsulfamide (3.12 g: 15.9 mmole), and azodicarboxylic acid diethylester (5.67 ml: 36 mmole) are successively added. The mixture is stirred under ice cooling for 55 minutes and at room temperature for 4 hours. The reaction mixture is dissolved in toluene (60 ml), concentrated, diluted with toluene (60 ml), filtered to remove separating crystals, and the filtrate is concentrated. The residue is purified by silica gel chromatography to give (2S,4S)-4-acetylthio-1-allyloxycarbonyl-2-(N-sulfamoyl-N-allyloxycarbonylamino)methylpyrrolidine (6.74 g). Yield: 55%. Colorless oil. concentrated diluted with toluene (60 ml) filtered to remove separating crystals the filtrate is concentrated The residue is purified by silica gel chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an argon atmosphere at -38° C., 0.77 ml of diethyl azodicarboxylate was added dropwise to 10 ml of an anhydrous tetrahydrofuran solution containing 550 mg of 3-(2-hydroxyethyl)imidazo[5,1-b]thiazole, 884 mg of N-allyloxycarbonyl-N-aminosulfonylamine and 1286 mg of triphenylphosphine, and the mixture was then stirred at -38° C. to -32° C. for 30 minutes and further stirred for 10 minutes while the solution was heated up to 0° C. The solvent was evaporated under reduced pressure to obtain an oil, and this oil was then dissolved in 50 ml of dichloromethane. Further, extraction was carried out with 2N hydrochloric acid (20 ml×2), and the combined aqueous layer was then washed with 10 ml of dichloromethane. Afterward, the solution was adjusted to pH 9 with anhydrous potassium carbonate, and then subjected to extraction with dichloromethane (30 ml×2). The dichloromethane extract was dried (anhydrous magnesium sulfate:anhydrous potassium carbonate=1:1) and then filtered, and the solvent was evaporated under reduced pressure. Afterward, the resulting oil was purified by a silica gel column chromatograph to obtain 548 mg of the title compound as a milky white amorphous. further stirred for 10 minutes while the solution The solvent was evaporated under reduced pressure to obtain an oil Further, extraction the combined aqueous layer was then washed with 10 ml of dichloromethane subjected to extraction with dichloromethane (30 ml×2) The dichloromethane extract was dried (anhydrous magnesium sulfate:anhydrous potassium carbonate=1:1) filtered the solvent was evaporated under reduced pressure Afterward, the resulting oil was purified by a silica gel column chromatograph

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

Procedure: Under an argon atmosphere at -37° C., 0.51 ml of diethyl azodicarboxylate was added dropwise to 6.7 ml of an anhydrous tetrahydrofuran solution containing 365 mg of 2-hydroxymethyl-3-methylimidazo[5,1-b]thiazole, 586 mg of N-allyloxycarbonyl-N-aminosulfonylamine and 854 mg of triphenylphosphine, and the mixture was then stirred at -37° C. to -20° C. for 110 minutes. The solvent was evaporated under reduced pressure to obtain an oil, and this oil was then suspended in 50 ml of dichloromethane. Further, the suspension was extracted with 2N hydrochloric acid (15 ml×2), and the combined aqueous layer was then washed with 20 ml of dichloromethane. After alkalified with anhydrous potassium carbonate, the solution was further extracted with dichloromethane (30 ml×3). The combined organic layer was washed with a semi-saturated saline solution, dried (anhydrous magnesium sulfate:anhydrous potassium carbonate=1:1), and then filtered, and the solvent was evaporated under reduced pressure. Afterward, the resulting oil was purified by a silica gel column chromatograph and successively Cephadex LH-20 to obtain 208.5 mg of the title compound as a milky white powder. The solvent was evaporated under reduced pressure to obtain an oil Further, the suspension was extracted with 2N hydrochloric acid (15 ml×2) the combined aqueous layer was then washed with 20 ml of dichloromethane the solution was further extracted with dichloromethane (30 ml×3) The combined organic layer was washed with a semi-saturated saline solution dried (anhydrous magnesium sulfate:anhydrous potassium carbonate=1:1) filtered the solvent was evaporated under reduced pressure Afterward, the resulting oil was purified by a silica gel column chromatograph and successively Cephadex LH-20

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

Procedure: To a solution of (2S,4S)-4-acetylthio-1-allyloxycarbonylpyrrolidine-2-methanol (8.02 g: ca. 30 mmole) in ethyl acetate (83 ml) under ice cooling, triphenylphosphine (9.44 g: 13.6 mmole), N-allyloxycarbonylsulfamide (3.12 g: 15.9 mmole), and azodicarboxylic acid diethylester (5.67 ml: 36 mmole) are successively added. The mixture is stirred under ice cooling for 55 minutes and at room temperature for 4 hours. The reaction mixture is dissolved in toluene (60 ml), concentrated, diluted with toluene (60 ml), filtered to remove separating crystals, and the filtrate is concentrated. The residue is purified by silica gel chromatography to give (2S,4S)-4-acetylthio-1-allyloxycarbonyl-2-(N-sulfamoyl-N-allyloxycarbonylamino)methylpyrrolidine (6.74 g). Yield: 55%. Colorless oil. NMR δ(CDCl3) ppm: 1.5 to 1.7(m, 1H), 2.35(s, 3H), 2.5 to 2.7(m, 1H), 3.19 (dd, J=6.3 Hz, J=11.5 Hz, 1H), 3.68 (dd, J=3.8 Hz, J=14.5 Hz, 1H), 3.9 to 4.3(m, 3H), 4.3 to 4.7(m, 5H), 5.2 to 5.4(m, 4H), 5.8 to 6.1(m, 4H). concentrated diluted with toluene (60 ml) filtered to remove separating crystals the filtrate is concentrated The residue is purified by silica gel chromatography