benzyl N-[(3S)-2-oxoazetidin-3-yl]carbamate

反応条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred suspension of (S)-(2-oxo-3-azetidinyl)carbamic acid, phenylmethyl ester (2.20 g; see example 1C) in 60 ml of dry tetrahydrofuran under nitrogen was warmed using a water bath at 40° C. until solution occurs. The solution was cooled to -75° C., and 7.4 ml of 1.35 M sec-butyl lithium in cyclohexane (10 mmol) was added. After stirring for 2 minutes, (methylsulfonyl) isocyanate (about 1.20 g) was added. This reaction was stirred at -75° C. for 10 minutes and poured into 100 ml of 0.5 M pH 5.5 monobasic potassium phosphate buffer. Ethyl acetate was added, and the pH was adjusted to 7. After several extractions with ethyl acetate, the aqueous layer was covered with ethyl acetate and adjusted to pH 2. Repeated extraction with ethyl acetate gave an acidic extract, which was dried (sodium sulfate) and evaporated to a residue (2.61 g). Chromatography of this residue on 250 g of silicAR CC-4 using dichloromethane and then 1% methanol in dichloromethane provided 1.82 g of product as a residue. was warmed at 40° C. This reaction was stirred at -75° C. for 10 minutes After several extractions with ethyl acetate extraction with ethyl acetate gave an acidic extract, which was dried (sodium sulfate) evaporated to a residue (2.61 g)

反応条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred suspension of (S)-(2-oxo-3-azetidinyl)carbamic acid, phenylmethyl ester (2.20 g; see example 1C) in 60 ml of dry tetrahydrofuran under nitrogen was warmed using a water bath at 40° C. until solution occurs. The solution was cooled to -75° C., and 7.4 ml of 1.35 M sec-butyl lithium in cyclohexane (10 mmol) was added. After stirring for 2 minutes, (methylsulfonyl) isocyanate (about 1.20 g) was added. This reaction was stirred at -75° C. for 10 minutes and poured into 100 ml of 0.5 M pH 5.5 monobasic potassium phosphate buffer. Ethyl acetate was added, and the pH was adjusted to 7. After several extractions with ethyl acetate, the aqueous layer was covered with ethyl acetate and adjusted to pH 2. Repeated extraction with ethyl acetate gave an acidic extract, which was dried (sodium sulfate) and evaporated to a residue (2.61 g). Chromatography of this residue on 250 g of silicAR CC-4 using dichloromethane and then 1% methanol in dichloromethane provided 1.82 g of product as a residue. was warmed at 40° C. This reaction was stirred at -75° C. for 10 minutes After several extractions with ethyl acetate extraction with ethyl acetate gave an acidic extract, which was dried (sodium sulfate) evaporated to a residue (2.61 g)

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

実験手順: (S)-(2-Oxo-3-azetidinyl)carbamic acid, phenylmethyl ester (220 mgs) was dissolved in dry tetrahydrofuran (10 ml) and stirred well under nitrogen. Triethylamine (139 μl) was added, followed by p-toluenesulfonyl isocyanate (153 μl, 1 mmol). After 2 to 3 hours of stirring a crystalline material starts to precipitate out. After 2 hours of further stirring, the solid was removed by filtration, washed with a small volume of acetonitrile and dried in vacuo. Yield of the triethylamine salt is 332 mg, melting point 128°-130° C. After 2 to 3 hours of stirring a crystalline material to precipitate out the solid was removed by filtration washed with a small volume of acetonitrile dried in vacuo

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

実験手順: (S)-(2-Oxo-3-azetidinyl)carbamic acid, phenylmethyl ester (220 mgs) was dissolved in dry tetrahydrofuran (10 ml) and stirred well under nitrogen. Triethylamine (139 μl) was added, followed by p-toluenesulfonyl isocyanate (153 μl, 1 mmol). After 2 to 3 hours of stirring a crystalline material starts to precipitate out. After 2 hours of further stirring, the solid was removed by filtration, washed with a small volume of acetonitrile and dried in vacuo. Yield of the triethylamine salt is 332 mg, melting point 128°-130° C. After 2 to 3 hours of stirring a crystalline material to precipitate out the solid was removed by filtration washed with a small volume of acetonitrile dried in vacuo

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

実験手順: A solution of 3.12 g of 1-[(acetyloxy)-2-methyl(propyl)]-2-oxo-(3S)-[[(phenylmethoxy)-carbonyl]amino]azetidine in 70 ml of methanol and 7 ml of water was cooled to -15° C. and 1.33 g of potassium carbonate and 349 mg of sodium borohydride was added. The reaction mixture was stirred at -15° C. -0° C. After the reaction was complete (about 2 hours), the mixture was neutralized to pH 7 with 2N HCl and concentrated in vacuo. The concentrate was adjusted to pH 5.8, saturated with salt and extracted with ethyl acetate (3 times). The organic layer was dried and evaporated in vacuo. The residue was combined with material from a similar experiment and triturated with ether to give 3.30 g of the title compound. (about 2 hours) concentrated in vacuo extracted with ethyl acetate (3 times) The organic layer was dried evaporated in vacuo triturated with ether

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

実験手順: A solution of 3.12 g of 1-[(acetyloxy)-2-methyl(propyl)]-2-oxo-(3S)-[[(phenylmethoxy)-carbonyl]amino]azetidine in 70 ml of methanol and 7 ml of water was cooled to -15° C. and 1.33 g of potassium carbonate and 349 mg of sodium borohydride was added. The reaction mixture was stirred at -15° C. -0° C. After the reaction was complete (about 2 hours), the mixture was neutralized to pH 7 with 2N HCl and concentrated in vacuo. The concentrate was adjusted to pH 5.8, saturated with salt and extracted with ethyl acetate (3 times). The organic layer was dried and evaporated in vacuo. The residue was combined with material from a similar experiment and triturated with ether to give 3.30 g of the title compound. (about 2 hours) concentrated in vacuo extracted with ethyl acetate (3 times) The organic layer was dried evaporated in vacuo triturated with ether

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred suspension of 1.00 g of (3S)-2-oxo-3-[[(phenylmethoxy)carbonyl]amino]-1-azetidinesulfonic acid, 8-hydroxyquinolinium salt in 75 ml of anhydrous ethanol under nitrogen was placed in a 95° C. oil bath. The mixture was refluxed for 20 minutes, then cooled to 20° C. with an ice water bath. The solvent was removed on the rotary evaporator (bath temperature ≥30° C.). The residue was taken up in 10 ml of water and 80 ml of ethyl acetate. About 600 mg of MgSO4 was added followed by 570 mg of sodium bicarbonate. The mixture was stirred to effect solution. The organic layer was separated, washed with 5 ml of water, and dried over MgSO4. The solvent was evaporated to afford a white solid, which was tranferred to a 25 ml flask with acetone. The acetone was removed in vacuo and the solid residue was suspended in ca. 5 ml of ethyl acetate. Ether (ca. 6 ml) was added and the mixture was stored for 60 minutes at 0° C. The solid was isolate by filtration, washed with ether, and dried in vacuo to afford 392 mg of the title compound as a white solid. was placed in a 95° C. The mixture was refluxed for 20 minutes The solvent was removed on the rotary evaporator (bath temperature ≥30° C.) About 600 mg of MgSO4 was added The organic layer was separated washed with 5 ml of water dried over MgSO4 The solvent was evaporated to afford a white solid, which The acetone was removed in vacuo Ether (ca. 6 ml) was added The solid was isolate by filtration washed with ether dried in vacuo

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred suspension of 1.00 g of (3S)-2-oxo-3-[[(phenylmethoxy)carbonyl]amino]-1-azetidinesulfonic acid, 8-hydroxyquinolinium salt in 75 ml of anhydrous ethanol under nitrogen was placed in a 95° C. oil bath. The mixture was refluxed for 20 minutes, then cooled to 20° C. with an ice water bath. The solvent was removed on the rotary evaporator (bath temperature ≥30° C.). The residue was taken up in 10 ml of water and 80 ml of ethyl acetate. About 600 mg of MgSO4 was added followed by 570 mg of sodium bicarbonate. The mixture was stirred to effect solution. The organic layer was separated, washed with 5 ml of water, and dried over MgSO4. The solvent was evaporated to afford a white solid, which was tranferred to a 25 ml flask with acetone. The acetone was removed in vacuo and the solid residue was suspended in ca. 5 ml of ethyl acetate. Ether (ca. 6 ml) was added and the mixture was stored for 60 minutes at 0° C. The solid was isolate by filtration, washed with ether, and dried in vacuo to afford 392 mg of the title compound as a white solid. was placed in a 95° C. The mixture was refluxed for 20 minutes The solvent was removed on the rotary evaporator (bath temperature ≥30° C.) About 600 mg of MgSO4 was added The organic layer was separated washed with 5 ml of water dried over MgSO4 The solvent was evaporated to afford a white solid, which The acetone was removed in vacuo Ether (ca. 6 ml) was added The solid was isolate by filtration washed with ether dried 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 (3S)-2-oxo-3-[[(phenylmethoxy)carbonyl]amino]-1-azetidinesulfonic acid, tetrabutylammonium salt in acetonitrile was added 8-hydroxyquinolinium p-toluenesulfonate. The mixture was refluxed, yielding the title compound as verified by thin layer chromatography (Merck silica gel 60F, ethyl acetate). The mixture was refluxed

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

実験手順: To a solution of (3S)-2-oxo-3-[[(phenylmethoxy)carbonyl]amino]-1-azetidinesulfonic acid, tetrabutylammonium salt in acetonitrile was added 8-hydroxyquinolinium p-toluenesulfonate. The mixture was refluxed, yielding the title compound as verified by thin layer chromatography (Merck silica gel 60F, ethyl acetate). The mixture was refluxed

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

実験手順: (3S)-2-Oxo-3-[[(phenylmethoxy)carbonyl]amino]-1-azetidinesulfonic acid, 8-hydroxyquinolinium salt (150 mg, 0.337 mmol) was added to acetonitrile (10 ml) and rapidly heated to reflux in a preheated oil bath. After refluxing for a total of 18 minutes, the mixture was cooled to room temperature, filtered through Celite, and solvent was removed in vacuo. The residue was extracted with an acetonitrile-ethyl acetate mixture and the extract chromatographed on a silica gel column (Mallinckrodt SilicAR CC-7). The desired product (31 mg) was eluted with a 5% acetonitrile:95% ethyl acetate mixture. rapidly heated to reflux in a preheated oil bath After refluxing for a total of 18 minutes filtered through Celite, and solvent was removed in vacuo The residue was extracted with an acetonitrile-ethyl acetate mixture the extract chromatographed on a silica gel column (Mallinckrodt SilicAR CC-7) The desired product (31 mg) was eluted with a 5% acetonitrile

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

実験手順: (3S)-2-Oxo-3-[[(phenylmethoxy)carbonyl]amino]-1-azetidinesulfonic acid, 8-hydroxyquinolinium salt (150 mg, 0.337 mmol) was added to acetonitrile (10 ml) and rapidly heated to reflux in a preheated oil bath. After refluxing for a total of 18 minutes, the mixture was cooled to room temperature, filtered through Celite, and solvent was removed in vacuo. The residue was extracted with an acetonitrile-ethyl acetate mixture and the extract chromatographed on a silica gel column (Mallinckrodt SilicAR CC-7). The desired product (31 mg) was eluted with a 5% acetonitrile:95% ethyl acetate mixture. rapidly heated to reflux in a preheated oil bath After refluxing for a total of 18 minutes filtered through Celite, and solvent was removed in vacuo The residue was extracted with an acetonitrile-ethyl acetate mixture the extract chromatographed on a silica gel column (Mallinckrodt SilicAR CC-7) The desired product (31 mg) was eluted with a 5% acetonitrile