3-methyloxolane-2,5-dione

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: The starting material is prepared as follows: The mixture of 28.5 g of 2-methylsuccinic anhydride, 23.5 g of 4-aminopyridine and 350 ml of xylene is refluxed on a water separator while stirring for 3.5 hours. The hot solution is decanted from some gummy residue, cooled, filtered, the residue suspended in 100 ml of boiling isopropanol and filtered off again, to yield the 3-methyl-1-(4-pyridyl)-pyrrolidin-2,5-dione melting at 119°-120°. The starting material is prepared The hot solution is decanted from some gummy residue cooled filtered filtered off again

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

実験手順: To a solution of 37.7 g (0.2 mole) of 1,1,4,4-tetramethyl-1,2,3,4-tetrahydro naphthalene and 22.82 g (0.2 mole) of methylsuccinic anhydride in 250 cm3 of anhydrous 1,2-dichloroethane, there are added, by portions, over a period of about 1 hour, 53.3 g (0.4 mole) of anhydrous aluminum chloride in a manner to maintain the temperature lower than or equal to 30° C. After stirring for 3 hours at ambient temperature, the reaction mixture is poured into 200 cm3 of ice water. The organic phase is decanted. The aqueous phase is again extracted twice with 100 cm3 of dichloromethane. The dichloroethane and dichloromethane phases are combined, washed with water, dried on sodium sulfate and concentrated under reduced pressure. The residue is taken up in 300 cm3 of hexane, filtered, successively washed three times with 200 cm3 of toluene and then recrystallized in isopropyl ether. After drying, 20.7 g of 4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro- 2-naphthyl)-4-oxo-2-methyl butyric acid in the form of a white solid whose melting point is 165° C. are obtained. The organic phase is decanted The aqueous phase is again extracted twice with 100 cm3 of dichloromethane washed with water dried on sodium sulfate concentrated under reduced pressure filtered successively washed three times with 200 cm3 of toluene recrystallized in isopropyl ether After drying

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

実験手順: To a solution of 37.7 g (0.2 mole) of 1,1,4,4-tetramethyl-1,2,3,4-tetrahydro naphthalene and 22.82 g (0.2 mole) of methylsuccinic anhydride in 250 cm3 of anhydrous 1,2-dichloroethane, there are added, by portions, over a period of about 1 hour, 53.3 g (0.4 mole) of anhydrous aluminum chloride in a manner to maintain the temperature lower than or equal to 30° C. After stirring for 3 hours at ambient temperature, the reaction mixture is poured into 200 cm3 of ice water. The organic phase is decanted. The aqueous phase is again extracted twice with 100 cm3 of dichloromethane. The dichloroethane and dichloromethane phases are combined, washed with water, dried on sodium sulfate and concentrated under reduced pressure. The residue is taken up in 300 cm3 of hexane, filtered, successively washed three times with 200 cm3 of toluene and then recrystallized in isopropyl ether. After drying, 20.7 g of 4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro- 2-naphthyl)-4-oxo-2-methyl butyric acid in the form of a white solid whose melting point is 165° C. are obtained. The organic phase is decanted The aqueous phase is again extracted twice with 100 cm3 of dichloromethane washed with water dried on sodium sulfate concentrated under reduced pressure filtered successively washed three times with 200 cm3 of toluene recrystallized in isopropyl ether After drying

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 114 g. of methyl-succinic anhydride and 80 g. of liquid sulfur trioxide are stirred and heated to 110° C. in an apparatus fitted with a condenser adequate to contain the low boiling sulfur trioxide. After 1 hour, the product is cooled to 25° C. and has an equivalent weight of about 65. It is stored as a solution in methyl methacrylate. fitted with a condenser adequate the product is cooled to 25° C.

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 114 g. of methyl-succinic anhydride and 80 g. of liquid sulfur trioxide are stirred and heated to 110° C. in an apparatus fitted with a condenser adequate to contain the low boiling sulfur trioxide. After 1 hour, the product is cooled to 25° C. and has an equivalent weight of about 65. It is stored as a solution in methyl methacrylate. fitted with a condenser adequate the product is cooled to 25° C.

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

実験手順: A stirred mixture of 4-(3-amino-4-fluorobenzyl)-2H-phthalazin-1-one (2.02 g, 7.5 mmol; prepared in a manner similar to that described in Example 23), 3-methyldihydrofuran-2,5-dione (0.856 g, 7.5 mmol) and toluene (100 ml) was heated under reflux for 2.5 hours (for the first 30 minutes of this period, traces of water in the mixture were removed by azeotropic distillation). The resulting solid was collected by filtration from the hot mixture, washed with toluene (20 ml) and dried in vacuo to give N-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-2-methylsuccinamic acid (1.91 g) as an off-white solid, m.pt. 140–144° C.; 250 MHz 1H-nmr (d6-DMSO) δ (ppm): 0.95 (d, 3H) (CH3), 2.2–2.6 (m, 3H) (—CH2CHMe-), 4.1 (s, 2H) (ArCH2—), 6.9–7.2 (m, 2H) (2×ArH), 7.6–7.9 (m, 4H) (4×ArH), 8.1 (d, 1H) (ArH), 9.55 (s, 1H) (chain CONH), 12.0 (br s, 1H) (CO2H), 12.5 (s, 1H) (ring CONH); m/z (M+H)+ 384, 100% purity. prepared in a manner similar to was heated under reflux for 2.5 hours (for the first 30 minutes of this period were removed by azeotropic distillation) The resulting solid was collected by filtration from the hot mixture washed with toluene (20 ml) dried in vacuo

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

実験手順: 3-Methyl-2-sulfosuccinic acid sodium salt was prepared as follows. 20 g Methylsuccinic anhydride was dissolved in 40 g 1,2-dichloroethane. 15.4 g solid sulfur trioxide was melted and added in portions to 140 g 1,2-dichloroethane in an addition funnel. The sulfur trioxide solution was added slowly to the anhydride solution and stirred overnight. 50 mL water was then added, followed by 7 g sodium hydroxide dissolved in 50 mL water. The layers were separated and the 1,2-dichloroethane layer was again extracted with 50 mL water. The combined water layers were stripped to give 42.2 g yellowish solid. 1H-NMR (D2O) 2.65-2.80 ppm m, 2.47-2.58 ppm m, 1.04 ppm d J=7.07 Hz. The layers were separated the 1,2-dichloroethane layer was again extracted with 50 mL water

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

実験手順: Desirable nonplasticizing monoanhydrides include maleic anhydride; succinic anhydride; and the one to six carbon alkyl, the chloro, the phenyl, the benzyl and the mono and dimethylbenzyl derivatives of maleic anhydride such as citraconic anhydride; itaconic anhydride; chloromaleic anhydride; methyl succinic anhydride; propylsuccinic anhydride, hexylsuccinic anhydride; phenylmaleic anhydride; α,α-dimethylbenzylsuccinic anhydride; and the like. Also desirable monoanhydrides include phthalic anhydride, tetrahydrophthalic anhydride, hexahydrophthalic anhydride, and their chloro, methyl and cyano derivatives, and the like, such as methyltrihydrophthalic anhydride; 1,2-dicarboxylic- 4-chlorocyclohexane anhydride; 1,2-dicarboxylic-4-cyanocyclohexane anhydride; and the like. Further desirable monoanhydrides include 1,2-dicarboxylic-cyclopentane; 1,2-dicarboxyliccycloheptane; and the three-ringed anhydrides formed by the Diels-Alder condensation of maleic anhydride with cyclopentene, furan, or their methyl derivatives, such as bicyclo(2.2.1)heptene-2,3-dicarboxylic anhydride (Nadic anhydride); a mixture of methylbicyclo(2.2.1)heptene-2,3-dicarboxylic anhydride isomers (Nadic methyl anhydride); 7-oxabicyclo(2.2.1)heptene-2,3-dicarboxylic anhydride; and the like.