2-methylidenebutanedioic acid

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

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

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: 8.75 g of Rhodacal™ A-246L and 875 g of deionized water were charged to a 3 liter three neck flask equipped with mechanical stirrer and dry ice-acetone condenser. The system was purged with nitrogen for 30 minutes. A monomer emulsion was obtained by mixing 455 g of distilled water, 8.75 g of Rhodacal™ A-246L, 70 g of ethyl acrylate, 14 g of itaconic acid, 616 g of vinylidene chloride and 13 g of 10% sodium persulfate with magnetic stirring. The reactor was immersed in a constant temperature bath at 35° C. 1.3 g of sodium persulfate, 2.6 g of sodium metabisulfite and 2 g of 1% ferrous sulfate were added to the reactor and then the monomer emulsion was pumped to the reactor over two hours. The latex was stirred one more hour and 1 ml each of t-butyl hydroperoxide(10%) and sodium formaldehyde bisulfite(10%) were added twice at 20 minute intervals and stirred one more hour. The latex was cooled and filtered. Glass transition temperature was 9° C. as measured by DSC, average particle size obtained from PCS was 60 nm and % solids was 32.3%. equipped with mechanical stirrer and dry ice-acetone condenser The system was purged with nitrogen for 30 minutes A monomer emulsion was obtained The reactor was immersed in a constant temperature bath at 35° C were added twice at 20 minute intervals The latex was cooled filtered

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Itaconic acid (650 g) and (S)-1-phenylethylamine (605 g) were suspended in 1,3-dimethylimidazolidinone (650 ml), and the suspension was stirred at 80° C. for 1 hr with heating, and further at 120° C. for 3 hr with heating. The mixture was cooled to room temperature, and water (4 l) was added. The precipitated crystals were collected by filtration and dried to give 950 g of 1-((S)-1-phenylethyl)-5-oxo-3-pyrrolidinecarboxylic acid. The crystals were recrystallized 3 times with isopropyl alcohol to give 156 g of (3S)-1-((S)-1-phenylethyl)-5-oxo-3-pyrrolidinecarboxylic acid. with heating further at 120° C. for 3 hr with heating The mixture was cooled to room temperature The precipitated crystals were collected by filtration dried

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

Procedure: 8.75 g of Rhodacal™ A-246L and 875 g of deionized water were charged to a 3 liter three neck flask equipped with mechanical stirrer and dry ice-acetone condenser. The system was purged with nitrogen for 30 minutes. A monomer emulsion was obtained by mixing 455 g of distilled water, 8.75 g of Rhodacal™ A-246L, 70 g of ethyl acrylate, 14 g of itaconic acid, 616 g of vinylidene chloride and 13 g of 10% sodium persulfate with magnetic stirring. The reactor was immersed in a constant temperature bath at 35° C. 1.3 g of sodium persulfate, 2.6 g of sodium metabisulfite and 2 g of 1% ferrous sulfate were added to the reactor and then the monomer emulsion was pumped to the reactor over two hours. The latex was stirred one more hour and 1 ml each of t-butyl hydroperoxide(10%) and sodium formaldehyde bisulfite(10%) were added twice at 20 minute intervals and stirred one more hour. The latex was cooled and filtered. Glass transition temperature was 9° C. as measured by DSC, average particle size obtained from PCS was 60 nm and % solids was 32.3%. equipped with mechanical stirrer and dry ice-acetone condenser The system was purged with nitrogen for 30 minutes A monomer emulsion was obtained The reactor was immersed in a constant temperature bath at 35° C were added twice at 20 minute intervals The latex was cooled filtered

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

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

Procedure: 4-Fluoroaniline (0.7 ml, 7.6 mmol) was added to 2-methylenebutanedioic acid (1.0 g, 7.6 mmol) in a sealed tube. The mixture was heated to 110 degrees for 3 hours after which a precipitate formed. The reaction was filtered and the solid was dissolved in ethyl acetate and concetrated to yield 1-(4-fluorophenyl)-5-oxopyrrolidine-3-carboxylic acid (M+1=223.8). The product was taken to next step without determining mass. The mixture was heated to 110 degrees for 3 hours after which a precipitate formed The reaction was filtered the solid was dissolved in ethyl acetate

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

Procedure: 4-Fluoroaniline (0.7 ml, 7.6 mmol) was added to 2-methylenebutanedioic acid (1.0 g, 7.6 mmol) in a sealed tube. The mixture was heated to 110 degrees for 3 hours after which a precipitate formed. The reaction was filtered and the solid was dissolved in ethyl acetate and concetrated to yield 1-(4-fluorophenyl)-5-oxopyrrolidine-3-carboxylic acid (M+1=223.8). The product was taken to next step without determining mass. The mixture was heated to 110 degrees for 3 hours after which a precipitate formed The reaction was filtered the solid was dissolved in ethyl acetate

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

Procedure: The product of step A is dissolved in 100 ml. of acetic acid, 3.3 g. of itaconic acid is added followed by 2.3 g. of dinitrogen tetraoxide in 10 ml. of acetic acid (the latter being added dropwise). After two hours, the mixture is poured into water and extracted with diethyl ether. The ether extracts are washed with dilute sodium bicarbonate solution, with saturated sodium chloride solution, then dried. Evaporation provides a solid which is dissolved in chloroform and chromatographically fractionated on silica gel, eluting with chloroform-carbon tetrachloride, then chloroform. The desired product elutes slowly with chloroform. It is washed with hot hexane, then recrystallized from a hexane-chloroform mixture to provide 5-methylsulfinylmethyl-2-nitro-3-phenylbenzofuran, m.p. 161°-163° C. This is the product of Example 19. extracted with diethyl ether The ether extracts are washed with dilute sodium bicarbonate solution, with saturated sodium chloride solution dried Evaporation provides a solid which eluting with chloroform-carbon tetrachloride It is washed with hot hexane recrystallized from a hexane-chloroform mixture

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

Procedure: The product of step A is dissolved in 100 ml. of acetic acid, 3.3 g. of itaconic acid is added followed by 2.3 g. of dinitrogen tetraoxide in 10 ml. of acetic acid (the latter being added dropwise). After two hours, the mixture is poured into water and extracted with diethyl ether. The ether extracts are washed with dilute sodium bicarbonate solution, with saturated sodium chloride solution, then dried. Evaporation provides a solid which is dissolved in chloroform and chromatographically fractionated on silica gel, eluting with chloroform-carbon tetrachloride, then chloroform. The desired product elutes slowly with chloroform. It is washed with hot hexane, then recrystallized from a hexane-chloroform mixture to provide 5-methylsulfinylmethyl-2-nitro-3-phenylbenzofuran, m.p. 161°-163° C. This is the product of Example 19. extracted with diethyl ether The ether extracts are washed with dilute sodium bicarbonate solution, with saturated sodium chloride solution dried Evaporation provides a solid which eluting with chloroform-carbon tetrachloride It is washed with hot hexane recrystallized from a hexane-chloroform mixture