ethyl 2-(2,5-dioxopyrrol-1-yl)acetate

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

Procedure: In a separable flask, glycine ethyl ester hydrochloride (reagent grade) (279 g, 2 mol) was mixed into acetic anhydride (reagent grade) (800 ml). Then, to the mixture was added dropwise over 3 hours a solution of maleic anhydride (reagent grade) (196 g. 2 mol) in acetic anhydride (600 ml), with stirring at room temperature. After the dropwise addition, stirring was carried out for another 1 hour, and the resulting precipitate was collected by suction filtration, washed with ion-exchanged water, and dried. The product obtained (382 g), triethylamine (reagent grade) (404 g, 4 mol), and toluene (1200 ml) were charged into a separable flask equipped with a Dean-Stark trap. Then, the mixture was subjected to reaction at 120° C. for 2 hours with stirring. During the reaction, the water formed was removed with the Dean-Stark trap. After the reaction, toluene (300 ml) was added and the mixture was washed three times with ion-exchanged water. Then, the organic phase obtained was collected and subjected to removal of the toluene by evaporation using an evaporator and a vacuum dryer to give ethyl maleimidoacetate (165 g). (Yield: ca. 38%. The production of ethyl maleimidoacetate was verified by GPC measurement. The presence of ethyl maleimidoacetate was verified by 1H-NMR measurement using DMSO-d6. This compound is referred to hereinafter as Compound A4). After the dropwise addition stirring the resulting precipitate was collected by suction filtration washed with ion-exchanged water dried were charged into a separable flask equipped with a Dean-Stark trap Then, the mixture was subjected to reaction at 120° C. for 2 hours with stirring During the reaction was removed with the Dean-Stark trap After the reaction, toluene (300 ml) was added the mixture was washed three times with ion-exchanged water Then, the organic phase obtained was collected subjected to removal of the toluene by evaporation an evaporator

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

Procedure: Reagents: Ph3P (1.31 g, 5 mmol), DEAD (0.8 ml, 5 mmol), ethyl glycollate (0.71 ml, 7.5 mmol) and maleimide (0.48 g, 5 mmol).

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

Procedure: In a separable flask, glycine ethyl ester hydrochloride (reagent grade) (279 g, 2 mol) was mixed into acetic anhydride (reagent grade) (800 ml). Then, to the mixture was added dropwise over 3 hours a solution of maleic anhydride (reagent grade) (196 g. 2 mol) in acetic anhydride (600 ml), with stirring at room temperature. After the dropwise addition, stirring was carried out for another 1 hour, and the resulting precipitate was collected by suction filtration, washed with ion-exchanged water, and dried. The product obtained (382 g), triethylamine (reagent grade) (404 g, 4 mol), and toluene (1200 ml) were charged into a separable flask equipped with a Dean-Stark trap. Then, the mixture was subjected to reaction at 120° C. for 2 hours with stirring. During the reaction, the water formed was removed with the Dean-Stark trap. After the reaction, toluene (300 ml) was added and the mixture was washed three times with ion-exchanged water. Then, the organic phase obtained was collected and subjected to removal of the toluene by evaporation using an evaporator and a vacuum dryer to give ethyl maleimidoacetate (165 g). (Yield: ca. 38%. The production of ethyl maleimidoacetate was verified by GPC measurement. The presence of ethyl maleimidoacetate was verified by 1H-NMR measurement using DMSO-d6. This compound is referred to hereinafter as Compound A4). After the dropwise addition stirring the resulting precipitate was collected by suction filtration washed with ion-exchanged water dried were charged into a separable flask equipped with a Dean-Stark trap Then, the mixture was subjected to reaction at 120° C. for 2 hours with stirring During the reaction was removed with the Dean-Stark trap After the reaction, toluene (300 ml) was added the mixture was washed three times with ion-exchanged water Then, the organic phase obtained was collected subjected to removal of the toluene by evaporation an evaporator

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

Procedure: Reagents: Ph3P (1.31 g, 5 mmol), DEAD (0.8 ml, 5 mmol), ethyl glycollate (0.71 ml, 7.5 mmol) and maleimide (0.48 g, 5 mmol).

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

Procedure: Reagents: Ph3P (1.31 g, 5 mmol), DEAD (0.8 ml, 5 mmol), ethyl glycollate (0.71 ml, 7.5 mmol) and maleimide (0.48 g, 5 mmol).

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

Procedure: In a separable flask, glycine ethyl ester hydrochloride (reagent grade) (279 g, 2 mol) was mixed into acetic anhydride (reagent grade) (800 ml). Then, to the mixture was added dropwise over 3 hours a solution of maleic anhydride (reagent grade) (196 g. 2 mol) in acetic anhydride (600 ml), with stirring at room temperature. After the dropwise addition, stirring was carried out for another 1 hour, and the resulting precipitate was collected by suction filtration, washed with ion-exchanged water, and dried. The product obtained (382 g), triethylamine (reagent grade) (404 g, 4 mol), and toluene (1200 ml) were charged into a separable flask equipped with a Dean-Stark trap. Then, the mixture was subjected to reaction at 120° C. for 2 hours with stirring. During the reaction, the water formed was removed with the Dean-Stark trap. After the reaction, toluene (300 ml) was added and the mixture was washed three times with ion-exchanged water. Then, the organic phase obtained was collected and subjected to removal of the toluene by evaporation using an evaporator and a vacuum dryer to give ethyl maleimidoacetate (165 g). (Yield: ca. 38%. The production of ethyl maleimidoacetate was verified by GPC measurement. The presence of ethyl maleimidoacetate was verified by 1H-NMR measurement using DMSO-d6. This compound is referred to hereinafter as Compound A4). After the dropwise addition stirring the resulting precipitate was collected by suction filtration washed with ion-exchanged water dried were charged into a separable flask equipped with a Dean-Stark trap Then, the mixture was subjected to reaction at 120° C. for 2 hours with stirring During the reaction was removed with the Dean-Stark trap After the reaction, toluene (300 ml) was added the mixture was washed three times with ion-exchanged water Then, the organic phase obtained was collected subjected to removal of the toluene by evaporation an evaporator