diethyl 3-oxopentanedioate

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: Compound 5-3 was made in a manner similar to Hall, H. K. Jr.; J. Am. Chem. Soc., 1957, 79, 5444-5447. Step 2a: Into a mixture of diethyl acetonedicarboxylate (103.6 g, 0.512 mol) and acetaldehyde (45.3 g, 1.33 mol) was bubbled ammonia gas until that liquid was saturated at −30° C. The solution was stored in freezer overnight. The yellow sludge was dissolved in dichloromethane (15 mL), filtered though silica gel and washed with EtOAc. The organic layer was concentrated to give diethyl 2,6-dimethyl-4-oxopiperidine-3,5-dicarboxylate as a thick yellow oil (92 g, 54%). Step 2b: A solution of the diester (90 g, 0.332 mol) in 10% aqueous hydrochloric acid solution (400 mL) was refluxed for overnight. Water was evaporated to yield 2,6-Dimethyl-4-piperidone/HCl, which was used for the next step without further purification. Step 2c: 2,6-Dimethyl-4-piperidone HCl salt (25.0 g, 0.153 mol) was partitioned into dioxane (250 mL) and H2O (250 mL), and sodium bicarbonate (50 g, 0.59 mol) was added in several portions. Boc anhydride (80 g, 0.37 mol) was added and the resulting reaction mixture was stirred at rt overnight. The reaction mixture was evaporated to remove dioxane. The residue was extracted with Et2O and the organic layer was washed with brine and dried over sodium sulfate. After evaporation, the crude product was purified by chromatography (gradient elution of 9-14% EtOAc in hexane) to give Compound 5-3 as a white solid (18.0 g, 52%, mixture of 70:30 trans:cis) (based on comparison to NMR spectra of trans Compound 5-3 reported by Beak, P.; Lee, W. K.; J. Org. Chem. 1993, 58, 1109-1117). MS (ES+) m/z 128 (M-Boc+1). was bubbled ammonia gas until that liquid was saturated at −30° C The yellow sludge was dissolved in dichloromethane (15 mL) filtered though silica gel washed with EtOAc The organic layer was concentrated

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

実験手順: Benzylamine (89.1 g, 0.83 moles) is added over 10 minutes to a suspension of 5 A powdered molecular sieves (270 g) and diethyl 1,3-acetonedicarboxylate (160 g) (0.79 moles) in 350 ml toluene (external cooling applied to control exotherm). The suspension is stirred at room temperature for 14-17 hours and then filtered to provide 2. The filter cake is washed with three portions of toluene. The combined filtrates may be used as in the subsequent ketene reaction. filtered to provide 2 The filter cake is washed with three portions of toluene The combined filtrates may be used as in the subsequent ketene reaction

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

実験手順: Crude t-butyl 5-(m-chlorophenyl)-2-hydroximino-3-oxopentanoate (43 g., 0.15 mol) and diethyl acetonedicarboxylate (28 ml, 30.3 g, 0.15 mol) are placed in a 1 liter round bottom flask and 250 ml of glacial acetic acid added. With stirring, 25 g (0.30 mol) anhydrous sodium acetate is added followed by 26 g Zn dust (94% fine, 0.364 mol) in a portionwise manner so that the exotherm does not bring the reaction to reflux. When addition is complete, the reaction is heated on a steam bath for one hour. The hot solution is then decanted from the residual zinc into 3 liters of ice water, and the resulting mixture is stirred vigorously until the oil solidifies. The mixture is then allowed to stand for 1.5 hours, and the solid is filtered. The solid is washed with water, dried in vacuo and recrystallized to give 21.5 g (31%) of ethyl 5-(t-butoxycarbonyl)-4-[2-(m-chlorophenyl)ethyl]-3-ethoxycarbonylpyrrole-2-acetate, M.P. 131°- 132°. the reaction to reflux When addition the reaction is heated on a steam bath for one hour The hot solution is then decanted from the residual zinc into 3 liters of ice water the resulting mixture is stirred vigorously until the oil the solid is filtered The solid is washed with water dried in vacuo recrystallized

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Conc. sulfuric acid (1.5 ml) was added to a mixture of 2-amino-4,5,3',4'-tetramethoxybenzophenone (50.0 g), diethyl acetonedicarboxylate (35.0 g) and acetic acid (400 ml), and the mixture was stirred at 100° C. for 2.5 hours. The reaction mixture was concentrated under reduced pressure. The residue was poured into water, neutralized with an aqueous saturated solution of sodium bicarbonate, and extracted with chloroform. The chloroform layer was washed with water and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residual crystals were recrystallized from acetone to give ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-3-ethoxycarbonylquinoline-2-acetate (48.8 g, 64%). Colorless prisms, mp. 146°-147° C. The reaction mixture was concentrated under reduced pressure The residue was poured into water extracted with chloroform The chloroform layer was washed with water dried over magnesium sulfate the solvent was evaporated under reduced pressure The residual crystals were recrystallized from acetone

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Conc. sulfuric acid (1.5 ml) was added to a mixture of 2-amino-4,5,3',4'-tetramethoxybenzophenone (50.0 g), diethyl acetonedicarboxylate (35.0 g) and acetic acid (400 ml), and the mixture was stirred at 100° C. for 2.5 hours. The reaction mixture was concentrated under reduced pressure. The residue was poured into water, neutralized with an aqueous saturated solution of sodium bicarbonate, and extracted with chloroform. The chloroform layer was washed with water and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residual crystals were recrystallized from acetone to give ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-3-ethoxycarbonylquinoline-2-acetate (48.8 g, 64%). Colorless prisms, mp. 146°-147° C. The reaction mixture was concentrated under reduced pressure The residue was poured into water extracted with chloroform The chloroform layer was washed with water dried over magnesium sulfate the solvent was evaporated under reduced pressure The residual crystals were recrystallized from acetone

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

実験手順: To 30.33 g (0.15 mol) of diethyl acetonedicarboxylate was added dropwise 11.8 g (0.19 mol) of cyclopropylamine at such a rate that reaction temperature was kept below 48° C. The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was poured into H2O, extracted twice with ether, dried (MgSO4) and concentrated in vacuo affording 34.42 g of a light yellow oil. Crude was kugelrohr distilled at 53 Pa and collected at a pot temperature of 102°-104° C. to give 23.73 g (66%) of enamine diester as a light yellow oiI nD25 5025. that reaction temperature was kept below 48° C extracted twice with ether dried (MgSO4) concentrated in vacuo

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

実験手順: To 30.33 g (0.15 mol) of diethyl acetonedicarboxylate was added dropwise 11.8 g (0.19 mol) of cyclopropylamine at such a rate that reaction temperature was kept below 48° C. The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was poured into H2O, extracted twice with ether, dried (MgSO4) and concentrated in vacuo affording 34.42 g of a light yellow oil. Crude was kugelrohr distilled at 53 Pa and collected at a pot temperature of 102°-104° C. to give 23.73 g (66%) of enamine diester as a light yellow oiI nD25 5025. that reaction temperature was kept below 48° C extracted twice with ether dried (MgSO4) concentrated in vacuo

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

実験手順: Diethyl 3-oxopentanedioate (45.5 ml, 0.25 mol) was added to a suspension of magnesium ethoxide (prepared from magnesium turnings (9 g, 0.375 mol) and iodine (0.1 g) in dry ethanol (275 ml)), and the mixture was heated under reflux for 90 min. 1-Bromo-2-methylpropane (54 ml, 0.5 mol) was added, and the reaction was heated under reflux for 16 h. Further 1-bromo-2-methylpropane (27 ml, 0.25 mol) was added to the boiling mixture, and after 3 h the solvent was evaporated in vacuo. The residue was partitioned between 2 N hydrochloric acid and ether. After extracting the aqueous phase with ether, the combined organics were washed successively with water, 5% sodium bicarbonate, water and brine, then were dried (Na2SO4) and evaporated in vacuo. The residue was distilled to give the title compound as a colourless oil (40 g, 62%), bp 118°-120° C. (1 mmHg). δ (CDCl3): 0.9 (6H, d, J=6Hz), 1.25 (6H, t, J=7Hz), 1.4-1.9 (3H, m), 3.5 (2H, s), 3.7 (1H, d, J=9Hz) and 4.2 (4H, q, J=7Hz). the mixture was heated under reflux for 90 min the reaction was heated under reflux for 16 h after 3 h the solvent was evaporated in vacuo The residue was partitioned between 2 N hydrochloric acid and ether After extracting the aqueous phase with ether the combined organics were washed successively with water, 5% sodium bicarbonate, water and brine were dried (Na2SO4) evaporated in vacuo The residue was distilled

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

実験手順: A suspension of 3-amino-s-triazole (28 g) and diethyl acetonedicarboxylate (100 g) in 100 ml of acetic acid was refluxed for six hours. After cooling to room temperature, 150 ml of concentrated hydrochloric acid was added under ice cooling, the crystals thus formed were collected by filtration, and washed twice with 100 ml of ethanol, then once with 100 ml of ether, affording 71 g of the objective compound as colorless crystals. was refluxed for six hours the crystals thus formed were collected by filtration washed twice with 100 ml of ethanol