1-ethylpiperidine-2,4-dione

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: 1-Ethyl-2,4-dioxopiperidine (1.06 g) is dissolved in N,N-dimethylformamide (50 ml), and the solution is added dropwise to a suspension of sodium hydride (60% dispersion in oil, 332 mg) in N,N-dimethylformamide (50 ml) under ice-cooling. The mixture is stirred for 20 minutes, and thereto is added 2-methylthio-1,3-dithiolium iodide (1.89 g). After stirring at room temperature overnight, the reaction mixture is poured onto water and extracted with ethyl acetate. The extract is washed with water, dried and distilled to remove the solvent. The residue is purified by silica gel column chromatography (developer: ethyl acetate) and then recrystallized from ethyl acetate-isopropyl ether to give 1-ethyl-3-(1,3-dithiol-2-ylidene)-2,4-dioxopiperidine (1.10 g) as pale yellow needles. m.p. 114.5°-117° C. cooling After stirring at room temperature overnight the reaction mixture is poured onto water extracted with ethyl acetate The extract is washed with water dried distilled to remove the solvent The residue is purified by silica gel column chromatography (developer: ethyl acetate) recrystallized from ethyl acetate-isopropyl ether

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

実験手順: 1-Ethyl-2,4-dioxopiperidine (1.06 g) is dissolved in N,N-dimethylformamide (50 ml), and the solution is added dropwise to a suspension of sodium hydride (60% dispersion in oil, 332 mg) in N,N-dimethylformamide (50 ml) under ice-cooling. The mixture is stirred for 20 minutes, and thereto is added 2-methylthio-1,3-dithiolium iodide (1.89 g). After stirring at room temperature overnight, the reaction mixture is poured onto water and extracted with ethyl acetate. The extract is washed with water, dried and distilled to remove the solvent. The residue is purified by silica gel column chromatography (developer: ethyl acetate) and then recrystallized from ethyl acetate-isopropyl ether to give 1-ethyl-3-(1,3-dithiol-2-ylidene)-2,4-dioxopiperidine (1.10 g) as pale yellow needles. m.p. 114.5°-117° C. cooling After stirring at room temperature overnight the reaction mixture is poured onto water extracted with ethyl acetate The extract is washed with water dried distilled to remove the solvent The residue is purified by silica gel column chromatography (developer: ethyl acetate) recrystallized from ethyl acetate-isopropyl ether

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

実験手順: Sodium hydride (in the form of a 60% dispersion in oil) (447 mg) is suspended in N,N-dimethylformamide (10 ml), and thereto is added dropwise a solution of 4-methoxy-5,6-dihydro-2(1H)-pyridone (1.29 g) in N,N-dimethylformamide (30 ml). The mixture is stirred under ice-cooling for 30 minutes, and thereto is added dropwise ethyl iodide (0.97 ml). The mixture is stirred under ice-cooling for 30 minutes and further at room temperature for 2.5 hours. The reaction mixture is poured onto water and extracted with chloroform. The extract is washed with a saturated sodium chloride solution and dried. After evaporating the solvent, the residue is dissolved in ethanol (120 ml) and thereto is added 10% hydrochloric acid (60 ml), and the mixture is allowed to stand at 25° C. for 5 hours. After distilling off the solvent under reduced pressure, the residue is dissolved in chloroform, washed with 5% aqueous sodium hydrogen carbonate solution and water, and then dried. The solvent is distilled off to give 1-ethyl-2,4-dioxopiperidine (1.12 g, 78%). cooling for 30 minutes The mixture is stirred under ice- The reaction mixture is poured onto water extracted with chloroform The extract is washed with a saturated sodium chloride solution dried After evaporating the solvent the residue is dissolved in ethanol (120 ml) is added 10% hydrochloric acid (60 ml) After distilling off the solvent under reduced pressure the residue is dissolved in chloroform washed with 5% aqueous sodium hydrogen carbonate solution and water dried The solvent is distilled off

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

実験手順: Added to 8.3 g of 1-ethylpiperidine-2,4-dione were 11 g of methyl orthoformate and 20 ml of acetic anhydride. The resultant mixture was refluxed for 7 hours. After allowing the reaction mixture to cool down, excess methyl orthoformate and acetic anydride were distilled off under reduced pressure. The brown residue was distilled under reduced pressure in a Kugelroll apparatus (0.5 mmHg; bath temperature: 200°-250° C.) to obtain 2.7 g of 1-ethyl-3-methoxymethylenepiperidine-2,4-dione as crystals (yield: 25%). The crystals were recrystallized from a mixed solvent of ethyl acetate and hexane to obtain needles. to cool down excess methyl orthoformate and acetic anydride were distilled off under reduced pressure The brown residue was distilled under reduced pressure in a Kugelroll apparatus (0.5 mmHg; bath temperature: 200°-250° C.)

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

実験手順: Added to 36.0 g of 3-carboethoxy-1-ethylpiperidine-2,4-dione (Referential Example 35) was 300 ml of a 10% aqueous solution of hydrochloric acid. The resultant mixture was refluxed for 40 minutes. After allowing the reaction mixture to cool down, it was extracted with chloroform. The chloroform layer was washed with water, dried and then concentrated, thereby obtaining 16.6 g of 1-ethylpiperidine-2,4-dione as a light yellowish oily substance (yield: 70%). to cool down it was extracted with chloroform The chloroform layer was washed with water dried concentrated

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: 11 g of methyl orthoformate and 20 ml of acetic anhydride were added to 8.3 g of 1-ethylpiperidine-2,4-dione, and they were refluxed for 7 hours and then allowed to cool. Excessive methyl orthoformate and acetic anhydride were removed by vacuum distillation. The resulting brown reside was subjected to vacuum distillation (0.5 mmHg, bath temperature of 200° to 250° C.) using a kugelrohr apparatus, whereby 2.7 g of 1-ethyl-3-methoxymethylenepiperidine-2,4-dione was obtained as a crystal with an yield of 25%. This crystal was recrystallized from a mixed solvent consisting of ethyl acetate and hexane to obtain a needle-like crystal of said compound. were refluxed for 7 hours to cool Excessive methyl orthoformate and acetic anhydride were removed by vacuum distillation The resulting brown reside was subjected to vacuum distillation (0.5 mmHg, bath temperature of 200° to 250° C.)

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

実験手順: 300 ml of a 10% aqueous hydrochloric acid solution was added to 36.0 g of 3-carboethoxy-1-ethylpiperidine-2,4-dione, and they were refluxed for 40 minutes and allowed to cool. The resulting mixture was subjected to extraction by chloroform. The resulting chloroform layer was water-washed, dried and concentrated to obtain 16.6 g of 1-ethylpiperidine-2,4-dione as a light yellow oily matter with an yield of 70%. were refluxed for 40 minutes to cool The resulting mixture was subjected to extraction by chloroform washed dried concentrated

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

実験手順: Sodium hydride (in the form of a 60% dispersion in oil) (447 mg) is suspended in N,N-dimethylformamide (10 ml), and thereto is added dropwise a solution of 4-methoxy-5,6-dihydro-2(1H)-pyridone (1.29 g) in N,N-dimethylformamide (30 ml). The mixture is stirred under ice-cooling for 30 minutes, and thereto is added dropwise ethyl iodide (0.97 ml). The mixture is stirred under ice-cooling for 30 minutes and further at room temperature for 2.5 hours. The reaction mixture is poured onto water and extracted with chloroform. The extract is washed with a saturated sodium chloride solution and dried. After evaporating the solvent, the residue is dissolved in ethanol (120 ml) and thereto is added 10% hydrochloric acid (60 ml), and the mixture is allowed to stand at 25° C. for 5 hours. After distilling off the solvent under reduced pressure, the residue is dissolved in chloroform, washed with 5% aqueous sodium hydrogen carbonate solution and water, and then dried. The solvent is distilled off to give 1-ethyl-2,4-dioxopiperidine (1.12 g, 78%). cooling for 30 minutes The mixture is stirred under ice- The reaction mixture is poured onto water extracted with chloroform The extract is washed with a saturated sodium chloride solution dried After evaporating the solvent the residue is dissolved in ethanol (120 ml) is added 10% hydrochloric acid (60 ml) After distilling off the solvent under reduced pressure the residue is dissolved in chloroform washed with 5% aqueous sodium hydrogen carbonate solution and water dried The solvent is distilled off

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

実験手順: 1-Ethyl-2,4-dioxopiperidine (1.06 g) is dissolved in N,N-dimethylformamide (50 ml), and the solution is added dropwise to a suspension of sodium hydride (60% dispersion in oil, 332 mg) in N,N-dimethylformamide (50 ml) under ice-cooling. The mixture is stirred for 20 minutes, and thereto is added 2-methylthio-1,3-dithiolium iodide (1.89 g). After stirring at room temperature overnight, the reaction mixture is poured onto water and extracted with ethyl acetate. The extract is washed with water, dried and distilled to remove the solvent. The residue is purified by silica gel column chromatography (developer: ethyl acetate) and then recrystallized from ethyl acetate-isopropyl ether to give 1-ethyl-3-(1,3-dithiol-2-ylidene)-2,4-dioxopiperidine (1.10 g) as pale yellow needles. m.p. 114.5°-117° C. cooling After stirring at room temperature overnight the reaction mixture is poured onto water extracted with ethyl acetate The extract is washed with water dried distilled to remove the solvent The residue is purified by silica gel column chromatography (developer: ethyl acetate) recrystallized from ethyl acetate-isopropyl ether

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

実験手順: Added to 8.3 g of 1-ethylpiperidine-2,4-dione were 11 g of methyl orthoformate and 20 ml of acetic anhydride. The resultant mixture was refluxed for 7 hours. After allowing the reaction mixture to cool down, excess methyl orthoformate and acetic anydride were distilled off under reduced pressure. The brown residue was distilled under reduced pressure in a Kugelroll apparatus (0.5 mmHg; bath temperature: 200°-250° C.) to obtain 2.7 g of 1-ethyl-3-methoxymethylenepiperidine-2,4-dione as crystals (yield: 25%). The crystals were recrystallized from a mixed solvent of ethyl acetate and hexane to obtain needles. to cool down excess methyl orthoformate and acetic anydride were distilled off under reduced pressure The brown residue was distilled under reduced pressure in a Kugelroll apparatus (0.5 mmHg; bath temperature: 200°-250° C.)