1-(4-溴丁基)吡咯烷-2-酮

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 9 g of 1-(4-bromobutyl)-2-pyrrolidinone and 7.6 g of 1-[6-(trifluoromethyl)-2-pyridinyl]-piperazine were mixed with 100 ml of butanol. 4.3 g of sodium carbonate were added, and the mixture is refluxed for 3 hours. The precipitate is filtered and washed with butanol, and the filtrate is then evaporated. The residue was dissolved in dichloromethane, washed with water, dried over anhydrous magnesium sulfate, after which the solvent was evaporated to obtain 12.5 g of 1-[4-[4-[6-(trifluoromethyl)-2-pyridinyl]-1-piperazinyl]-butyl]-2-pyrrolidinone. To make the monofumarate, the free base was mixed with 3.9 g of fumaric acid in absolute ethanol. The resulting substance was recrystallized twice from absolute ethanol, after which 7.8 g (43.6% yield) of 1-[4-[4-[6-(trifluoromethyl)-2-pyridinyl]-1-piperazinyl]butyl]-2pyrrolidinone. (E)-2-butenedioate (1:1) salt were obtained. M.p. 173° C. the mixture is refluxed for 3 hours The precipitate is filtered washed with butanol the filtrate is then evaporated The residue was dissolved in dichloromethane washed with water dried over anhydrous magnesium sulfate after which the solvent was evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2 7 g of 1-(4-bromobutyl)-2-pyrrolidinone were mixed with 2.2 g of 1-[4-(trifluoromethyl)-2-pyridinyl]piperazine dissolved in 30 ml of butanol, after which 1.3 g of sodium carbonate were added. The mixture was refluxed for 2 hours, after which the precipitate was filtered and washed with butanol. The solvent was evaporated and the residue was dissolved in dichloromethane, washed with water, and dried over anhydrous magnesium sulfate. After evaporation of the solvent 3.4 g of 1-[4-[4-[4-(trifluoromethyl)-2-pyridinyl]-1-piperazinyl]butyl]-2-pyrrolidinone were obtained. To make the monofumarate, 1 g of fumaric acid dissolved in absolute ethanol was mixed with the free base. The resulting compound was recrystallized twice from acetonitrile, after which 2.4 g (52% yield) of 1-[4-[4-[4-(trifluoromethyl)-2-pyridinyl]-1-piperazinyl]butyl]-2pyrrolidinone (E)-2-butenedioate (1:1) salt were obtained with a melting point of 140° C. The mixture was refluxed for 2 hours after which the precipitate was filtered washed with butanol The solvent was evaporated the residue was dissolved in dichloromethane washed with water dried over anhydrous magnesium sulfate After evaporation of the solvent 3.4 g of 1-[4-[4-[4-(trifluoromethyl)-2-pyridinyl]-1-piperazinyl]butyl]-2-pyrrolidinone were obtained was mixed with the free base The resulting compound was recrystallized twice from acetonitrile

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of 37 g of powdered KOH in 500 ml of tetrahydrofuran (THF) were added 25.2 g of tetraethylammonium bromide. Then, a solution of 51.6 g of 2-pyrrolidinone and 129.6 g of 1,4-dibromobutane in 100 ml of THF was added dropwise to the mixture. The mixture was heated and refluxed for 2 hours. The precipitate was filtered, and the THF evaporated. The residue was dissolved in dichloromethane, washed with water, and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue distilled to yield 51.2 g of 1-(4-bromobutyl)-2-pyrrolidinone (38.8% yield) having a boiling point of 120° C. at 0.05 mm Hg. The mixture was heated refluxed for 2 hours The precipitate was filtered the THF evaporated The residue was dissolved in dichloromethane washed with water dried over anhydrous magnesium sulfate The solvent was evaporated the residue distilled

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 1-(4-bromobutyl)-2-pyrrolidinone (2.0 g/9.1 mmol) and benzylpiperazine (1.58 ml/9.1 mmol) in ethanol (4.5 ml) was stirred overnight at ambient temperature. The mixture was basified with 2 N NaOH and extracted with dichloromethane (50 ml×2). The combined extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by column chromatography (100 g/dichloromethane=100:5-100:10) to give a pale yellow oil (1.6 g/56%). extracted with dichloromethane (50 ml×2) The combined extracts were washed with brine dried over magnesium sulfate filtered concentrated The residue was purified by column chromatography (100 g/dichloromethane=100:5-100:10) to give a pale yellow oil (1.6 g/56%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of sodium hydride(555 mg/13.9 mmol) in tetrahydrofuran (50 ml) was added 2-pyrrolidinone (0.7 ml/9.26 mmol) at ice-cooling temperature. The mixture was stirred for 1 h at ambient temperature, and then 1,4-dibromobutane (10 g/46.3 mmol) was added at the same temperature. The resulting mixture was stirred overnight. Water (10 ml) was added to the mixture and the mixture was extracted with ethyl acetate (50 ml×2). The combined extracts were washed with water and brine succesively, then dried over magnesium sulfate, filtered and concentrated. The residue was purified by column chromatography (80g/dichloromethane:methanol=100:0-100:5-100:10) to give a colorless oil(2.0 g/90%). cooling temperature The resulting mixture was stirred overnight the mixture was extracted with ethyl acetate (50 ml×2) The combined extracts were washed with water and brine succesively dried over magnesium sulfate filtered concentrated The residue was purified by column chromatography (80g/dichloromethane:methanol=100:0-100:5-100:10) to give a colorless oil(2.0 g/90%)