2-(5-bromopentyl)isoindole-1,3-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:

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: Potassium phthalimide (92.5 g) was added in six portions over 4 hours to a boiling solution of 1,5-dibromopentane (230 g) in acetone (670 ml). The mixture was boiled under reflux for 24 hours, then cooled and filtered. The filtrate was evaporated to dryness and the residue dissolved in petroleum ether, b.p. 60-80° C. ethyl acetate (1:1) and the solution filtered. The filtrate was evaporated to dryness and the residue washed with several portions of petroleum ether, b.p. 60-80° C. to remove excess dibromopentane. The remaining oil was dried under vacuum at 50° C. The petrol washings were evaporated to dryness and distilled under vacuum to give recovered dibromopentane and a second fraction b.p. 86-120° C. at 17 mbar. This fraction solidified on cooling and scratching. A little of this solid was used to seed the remaining oil and the combined solids were recrystallised from absolute ethanol (300 ml) to give N-(5-bromopentyl)phthalimide, m.p. 62-63° C. under reflux for 24 hours cooled filtered The filtrate was evaporated to dryness the residue dissolved in petroleum ether b.p. 60-80° C. ethyl acetate (1:1) and the solution filtered The filtrate was evaporated to dryness the residue washed with several portions of petroleum ether, b.p. 60-80° C. to remove excess dibromopentane The remaining oil was dried under vacuum at 50° C The petrol washings were evaporated to dryness distilled under vacuum to give recovered dibromopentane on cooling the combined solids were recrystallised from absolute ethanol (300 ml)

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

実験手順: N-(5-Bromopentyl)phthalimide (60 g) was added to a solution of 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamide dihydrochloride (75.1 g) and potassium carbonate (112 g) in dimethylformamide (800 ml), and the mixture was stirred at 75°-80° C. for 8 hr. Insoluble matter was filtered off and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform:methanol=10:1) to give 60.2 g of 4-amino-5-chloro-N-(1-(5-(2,3-dihydro-1,3-dioxo-1H-isoindol-2-yl)pentyl)piperidin-4-ylmethyl)-2-methoxybenzamide. Insoluble matter was filtered off the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography (chloroform:methanol=10:1)

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

実験手順: Sodium (0.5 g) was dissolved in ethanol (7 ml) and diethyl propylmalonate (4.4 g) was added to the solution. The resulting mixture was heated under reflux for 15 minutes. To the mixture was added N-(5-bromopentyl)phthalimide (6.4 g) and the mixture was further heated under reflux for 4 hours. Then, ethanol was removed by distillation. The residue was treated with ether and filtered. The filtrate was concentrated and the residue was chromatographed on silica gel column. A fraction eluted with 5% methanol in chloroform was recrystallized from a mixture of ether and hexane to give colorless crystals of diethyl 2-(5-phthalimidopentyl)-2-propylmalonate (m.p. 51°-52° C., yield 3.7 g). The resulting mixture was heated under reflux for 15 minutes the mixture was further heated under reflux for 4 hours Then, ethanol was removed by distillation The residue was treated with ether filtered The filtrate was concentrated the residue was chromatographed on silica gel column A fraction eluted with 5% methanol in chloroform was recrystallized from a mixture of ether and hexane

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

実験手順: Potassium phthalimide (92.5 g) was added in six portions over 4 hours to a boiling solution of 1,5-dibromopentane (230 g) in acetone (670 ml). The mixture was boiled under reflux for 24 hours, then cooled and filtered. The filtrate was evaporated to dryness and the residue dissolved in petroleum ether, b.p. 60-80° C./ethyl acetate (1:1) and the solution filtered. The filtrate was evaporated to dryness and the residue washed with several portions of petroleum ether, b.p. 60-80° C. to remove excess dibromopentane. The remaining oil was dried under vacuum at 50° C. The petrol washings were evaporated to dryness and distilled under vacuum to give recovered dibromopentane and a second fraction b.p. 86-120° C. at 17 mbar. This fraction solidified on cooling and scratching. A little of this solid was used to seed the remaining oil and the combined solids were recrystallised from absolute ethanol (300 ml) to give N-(5-bromopentyl)phthalimide, m.p. 62-63° C. under reflux for 24 hours cooled filtered The filtrate was evaporated to dryness the residue dissolved in petroleum ether b.p. 60-80° C./ethyl acetate (1:1) and the solution filtered The filtrate was evaporated to dryness the residue washed with several portions of petroleum ether, b.p. 60-80° C. to remove excess dibromopentane The remaining oil was dried under vacuum at 50° C The petrol washings were evaporated to dryness distilled under vacuum to give recovered dibromopentane on cooling the combined solids were recrystallised from absolute ethanol (300 ml)