3-bromopyrrolidin-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 15.8 g of ethyl (Z)-2-(2-tritylaminothiazol-4-yl)-2-hydroxyiminoacetate are dissolved, in 70 ml of dimethylsulfoxide, and 5.8 g of anhydrous potassium carbonate are added thereto. The mixture is stirred at room temperature for 20 minutes. 6.6 g of 3-bromo-2-pyrrolidone are added to said mixture, and the mixture is stirred at room temperature for 20 hours. The mixture is poured into 800 ml of water, and crystalline precipitates are collected by filtration and washed with water. The crystals are dissolved in chloroform, washed with water and then dried. Then, the chloroform solution is evaporated under reduced pressure to remove solvent. 100 ml of ethyl acetate are added to the residue, and allowed to stand at room temperature. Crystalline precipitates thus obtained are collected by filtration and dried. 16.0 g of ethyl (Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetate are obtained. the mixture is stirred at room temperature for 20 hours crystalline precipitates are collected by filtration washed with water The crystals are dissolved in chloroform washed with water dried Then, the chloroform solution is evaporated under reduced pressure to remove solvent 100 ml of ethyl acetate are added to the residue to stand at room temperature Crystalline precipitates thus obtained are collected by filtration dried

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

Procedure: 10.9 g of ethyl (Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetate are dissolved in 25 ml of dimethylsulfoxide, and a solution of 14 g of anhydrous potassium carbonate in 13 ml of water is added thereto at a temperature of 15° to 20° C. The mixture is stirred at the same temperature for 20 minutes. 10 g of 3-bromo-2-pyrrolidone are added to said mixture at room temperature, and the mixture is stirred at the same temperature for 1.5 hours. 120 ml of water are added to the reaction mixture, and the aqueous mixture is stirred with ice-cooling. Crystalline precipitates are collected by filtration, and the crystals are washed with water and then dried at 40° C. 13 g of ethyl (Z)-2-(2-aminothiazol-4-yl)-2-[(2-pyrrolidon-3yl)oxyimino]acetate are obtained. The physico-chemical properties of this product are identical sith those of the product obtained in Example 2-(3). at a temperature of 15° to 20° C at room temperature the mixture is stirred at the same temperature for 1.5 hours the aqueous mixture is stirred with ice- cooling Crystalline precipitates are collected by filtration the crystals are washed with water dried at 40° C

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

Procedure: 31.8 g of ethyl 2-hydroxyimino-3-oxo-n-butyrate are dissolved in 150 ml of acetone, and 83 g of anhydrous potassium carbonate are added thereto. 33 g of 3-bromo-2-pyrrolidone are added to the mixture at 20° to 25° C. with stirring, and the mixture is stirred at the same temperature for one hour. One liter of ice-water is added to said mixture, and the aqueous mixture is extracted with ethyl acetate. The extract is dried and concentrated under reduced pressure to remove solvent. The residue is crystallized with diisopropyl ether, and the crystals are collected by filtration. The crystals are recrystallized from ethyl acetate. 32 g of ethyl (Z)-2-[(2-pyrrolidon-3-yl)-oxyimino]-3-oxo-n-butyrate are obtained as colorless needles. the mixture is stirred at the same temperature for one hour the aqueous mixture is extracted with ethyl acetate The extract is dried concentrated under reduced pressure to remove solvent The residue is crystallized with diisopropyl ether the crystals are collected by filtration The crystals are recrystallized from ethyl acetate

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

Procedure: Substantially in the same manner as in Example 39 (1), 8.2 g (50 mmol) of 3-bromopyrrolidin-2-one and 9.91 g (55 mmol) of N-dimethylaminophenylcarbamate in 100 ml of pyridine were treated to give 7.96 g of the objective compound as white crystal in 63.6% yield.

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

Procedure: Substantially in the same manner as in Example 39 (1), 8.2 g (50 mmol) of 3-bromopyrrolidin-2-one and 9.91 g (55 mmol) of N-dimethylaminophenylcarbamate in 100 ml of pyridine were treated to give 7.96 g of the objective compound as white crystal in 63.6% yield.

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 16.0 g (91 mmol) of 3-bromopyrrolidin-2-one were heated to boiling in 30 ml of acetic anhydride for 1 hour. After evaporating the reaction mixture t dryness under reduced pressure, the residue was dissolved in 50 ml of tetrahydrofuran and, after adding 26.2 g (0.1 mol) of triphenylphosphine, heated under reflux for 5 hours. It was then concentrated again, the residue was dissolved in 300 ml of ethanol and 24.7 g (78 mmol) of the aldehyde from Example 2 b1) and 27 ml (0.36 mol) of triethylamine were added. After heating the mixture at 70° C. for 2 hours, the yellow precipitate was filtered off and washed with ethanol. The crystal magma is dissolved in about 2 1 of chloroform, the solution is washed several times with saturated sodium chloride solution and dried over Na2SO4, and the chloroform phase is concentrated to a third. Yellow crystals deposit on allowing to stand for a relatively long time. After evaporating the reaction mixture t dryness under reduced pressure the residue was dissolved in 50 ml of tetrahydrofuran heated under reflux for 5 hours It was then concentrated again the residue was dissolved in 300 ml of ethanol the yellow precipitate was filtered off washed with ethanol The crystal magma is dissolved in about 2 1 of chloroform the solution is washed several times with saturated sodium chloride solution dried over Na2SO4 the chloroform phase is concentrated to a third

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

Procedure: 15.8 g of ethyl (Z)-2-(2-tritylaminothiazol-4-yl)-2hydroxyiminoacetate are dissolved in 70 ml of dimethylsulfoxide, and 5.8 g of anhydrous potassium carbonate are added thereto. The mixture is stirred at room temperature for 20 minutes. 6.6 g of 3-bromo-2-pyrrolidone are added to said mixture, and the mixture is stirred at room temperature for 20 hours. The mixture is poured into 800 ml of water, and crystalline precipitates are collected by filtration and washed with water. The crystals are dissolved in chloroform, washed with water and then dried. Then, the chloroform solution is evaporated under reduced pressure to remove solvent. 100 ml of ethyl acetate are added to the residue, and allowed to stand at room temperature. Crystalline precipitates thus obtained are collected by filtration and dried. 16.0 g of ethyl (Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetate are obtained. the mixture is stirred at room temperature for 20 hours crystalline precipitates are collected by filtration washed with water The crystals are dissolved in chloroform washed with water dried Then, the chloroform solution is evaporated under reduced pressure to remove solvent 100 ml of ethyl acetate are added to the residue to stand at room temperature Crystalline precipitates thus obtained are collected by filtration dried

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

Procedure: 15.8 g of ethyl (Z)-2-(2-tritylaminothiazol-4-yl)-2hydroxyiminoacetate are dissolved in 70 ml of dimethylsulfoxide, and 5.8 g of anhydrous potassium carbonate are added thereto. The mixture is stirred at room temperature for 20 minutes. 6.6 g of 3-bromo-2-pyrrolidone are added to said mixture, and the mixture is stirred at room temperature for 20 hours. The mixture is poured into 800 ml of water, and crystalline precipitates are collected by filtration and washed with water. The crystals are dissolved in chloroform, washed with water and then dried. Then, the chloroform solution is evaporated under reduced pressure to remove solvent. 100 ml of ethyl acetate are added to the residue, and allowed to stand at room temperature. Crystalline precipitates thus obtained are collected by filtration and dried. 16.0 g of ethyl (Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetate are obtained. the mixture is stirred at room temperature for 20 hours crystalline precipitates are collected by filtration washed with water The crystals are dissolved in chloroform washed with water dried Then, the chloroform solution is evaporated under reduced pressure to remove solvent 100 ml of ethyl acetate are added to the residue to stand at room temperature Crystalline precipitates thus obtained are collected by filtration dried

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

Procedure: 15.8 g of ethyl (Z)-2-(2-tritylaminothiazol-4-yl)-2-hydroxyiminoacetate are dissolved in 70 ml of dimethylsulfoxide, and 5.8 g of anhydrous potassium carbonate are added thereto. The mixture is stirred at room temperature for 20 minutes. 6.6 g of 3-bromo-2-pyrrolidone are added to said mixture, and the mixture is stirred at room temperature for 20 hours. The mixture is poured into 800 ml of water, and crystalline precipitates are collected by filtration and washed with water. The crystals are dissolved in chloroform, washed with water and then dried. Then, the chloroform solution is evaporated under reduced pressure to remove solvent. 100 ml of ethyl acetate are added to the residue, and allowed to stand at room temperature. Crystalline precipitates thus obtained are collected by filtration and dried. 16.0 g of ethyl (Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetate are obtained. the mixture is stirred at room temperature for 20 hours crystalline precipitates are collected by filtration washed with water The crystals are dissolved in chloroform washed with water dried Then, the chloroform solution is evaporated under reduced pressure to remove solvent 100 ml of ethyl acetate are added to the residue to stand at room temperature Crystalline precipitates thus obtained are collected by filtration dried

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

Procedure: 15.8 g of ethyl (Z)-2-(2-tritylaminothiazol-4-yl)-2-hydroxyiminoacetate are dissolved, in 70 ml of dimethylsulfoxide, and 5.8 g of anhydrous potassium carbonate are added thereto. The mixture is stirred at room temperature for 20 minutes. 6.6 g of 3-bromo-2-pyrrolidone are added to said mixture, and the mixture is stirred at room temperature for 20 hours. The mixture is poured into 800 ml of water, and crystalline precipitates are collected by filtration and washed with water. The crystals are dissolved in chloroform, washed with water and then dried. Then, the chloroform solution is evaporated under reduced pressure to remove solvent. 100 ml of ethyl acetate are added to the residue, and allowed to stand at room temperature. Crystalline precipitates thus obtained are collected by filtration and dried. 16.0 g of ethyl (Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetate are obtained. the mixture is stirred at room temperature for 20 hours crystalline precipitates are collected by filtration washed with water The crystals are dissolved in chloroform washed with water dried Then, the chloroform solution is evaporated under reduced pressure to remove solvent 100 ml of ethyl acetate are added to the residue to stand at room temperature Crystalline precipitates thus obtained are collected by filtration dried