(3S)-3-benzylpiperazine-2,5-dione

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

実験手順: At ice-bath temperature, lithium aluminium hydride (1.6 g, 42.16 mmol) was added in portions to a stirring mixture of (S)-2-benzyl piperazine-3,6-dione (3.0 g, 14.70 mmol) and tetrahydrofuran (80 ml). After 30 min at ice-bath temperature, the mixture was refluxed for 4 h with stirring. The reaction was quenched by the portionwise addition of sodium sulfate decahydrate and some methanol until hydrogen evolution ceased. It was filtered and the solids were washed several times with dichloromethane. The combined filtrates were evaporated to leave a white solid. MS (m/z): 177.1 (M+H)+; C11H16N2 requir. 176.3. the mixture was refluxed for 4 h The reaction was quenched by the portionwise addition of sodium sulfate decahydrate It was filtered the solids were washed several times with dichloromethane The combined filtrates were evaporated to leave a white solid

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

実験手順: A solution of 23.30 g (62.91 mmol) N-Benzyloxycarbonyl-phenylalanine-glycine-methylester (obtained above) in 650 ml dry methanol was hydrogenated by adding Pd/C-catalyst and stirring the resulting mixture under H2 at r.t. for 3 h. After that, the mixture was filtered through celite and then half of the solvent was evaporated. The remaining solution was refluxed for 17 h. Filtration of the white precipitate and washing it twice with methanol yielded 10.71 g (52.45 mmol, 83.37%) 6-(S)-Benzyl-piperazine-2,5-dione as a white solid. After that, the mixture was filtered through celite half of the solvent was evaporated The remaining solution was refluxed for 17 h Filtration of the white precipitate washing it twice with methanol

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

実験手順: Lithium aluminum hydride (1.6 g, 42.16 mmol) was added in portions to a stirred mixture of (S)-2-benzyl piperazine-3,6-dione (3.0 g, 14.70 mmol) and tetrahydrofuran (80 ml) at 0° C. After 30 min at ice-bath temperature, the mixture was refluxed for 4 h with stirring. The reaction was quenched by the portionwise addition of sodium sulfate decahydrate and some methanol until hydrogen evolution ceased. It was filtered and the solids were washed several times with dichloromethane. The combined filtrates were evaporated to leave a white solid. the mixture was refluxed for 4 h The reaction was quenched by the portionwise addition of sodium sulfate decahydrate It was filtered the solids were washed several times with dichloromethane The combined filtrates were evaporated to leave a white solid

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2.3 g of 3-(S)-benzyl-piperazine-2,5-dione were suspended in anhydrous THF under nitrogen and cooled in an ice-bath. 4 equiv. of lithium aluminium hydride were added. The reaction was stirred at 0° C. for 0.5 h, then heated to reflux overnight. The reaction was quenched by the subsequent addition of 1 mL/gLiAlH4 of water, 1 mL/gLiAlH4 of 5% aqueous sodium hydroxide solution and 3 mL/gLiAlH4 of water. The resulting solid were separated by filtration through Celite and rinsed with ethyl acetate. The filtrate was concentrated in vacuo to afford 1.6 g of 2-(S)-benzylpiperazine as yellow oil. ES MS (+) m/z 177 cooled in an ice-bath heated to reflux overnight The reaction was quenched by the subsequent addition of 1 mL/gLiAlH4 of water, 1 mL/gLiAlH4 of 5% aqueous sodium hydroxide solution and 3 mL/gLiAlH4 of water The resulting solid were separated by filtration through Celite rinsed with ethyl acetate The filtrate was concentrated in vacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2.3 g of 3-(S)-benzyl-piperazine-2,5-dione were suspended in anhydrous THF under nitrogen and cooled in an ice-bath. 4 equiv. of lithium aluminium hydride were added. The reaction was stirred at 0° C. for 0.5 h, then heated to reflux overnight. The reaction was quenched by the subsequent addition of 1 mL/gLiAlH4 of water, 1 mL/gLiAlH4 of 5% aqueous sodium hydroxide solution and 3 mL/gLiAlH4 of water. The resulting solid were separated by filtration through Celite and rinsed with ethyl acetate. The filtrate was concentrated in vacuo to afford 1.6 g of 2-(S)-benzylpiperazine as yellow oil. ES MS (+) m/z 177 cooled in an ice-bath heated to reflux overnight The reaction was quenched by the subsequent addition of 1 mL/gLiAlH4 of water, 1 mL/gLiAlH4 of 5% aqueous sodium hydroxide solution and 3 mL/gLiAlH4 of water The resulting solid were separated by filtration through Celite rinsed with ethyl acetate The filtrate was concentrated in vacuo

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

実験手順: Lithium aluminium hydride (1.6 g, 42.16 mmol) was added in portions to a stirred mixture of (S)-2-benzylpiperazine-3,6-dione (3.0 g, 14.70 mmol) and tetrahydrofuran (80 ml) at 0° C. After 30 min at ice-bath temperature, the mixture was refluxed for 4 h with stirring. The reaction was quenched by the portionwise addition of sodium sulfate decahydrate and some methanol until hydrogen evolution ceased. It was filtered and the solids were washed several times with dichloromethane. The combined filtrates were evaporated to leave a white solid. MS (m/z): 177.1 (M+H)+; C11H16N2 requir. 176.3. the mixture was refluxed for 4 h The reaction was quenched by the portionwise addition of sodium sulfate decahydrate It was filtered the solids were washed several times with dichloromethane The combined filtrates were evaporated to leave a white solid

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

実験手順: At ice-bath temperature, lithium aluminium hydride (1.6 g, 42.16 mmol) was added in portions to a stirring mixture of (S)-2-benzylpiperazine-3,6-dione (3.0 g, 14.70 mmol) (comm. avail.) and tetrahydrofuran (80 ml). After 30 min at ice-bath temperature, the mixture was refluxed for 4 h with stirring. The reaction was quenched by the portionwise addition of sodium sulfate decahydrate and some methanol until hydrogen evolution ceased. It was filtered and the solids were washed several times with dichloromethane. The combined filtrates were evaporated to leave a white solid.MS (m/z): 177.1 (M+H)+; C11H16N2 requir. 176.3. the mixture was refluxed for 4 h The reaction was quenched by the portionwise addition of sodium sulfate decahydrate It was filtered the solids were washed several times with dichloromethane The combined filtrates were evaporated to leave a white solid.MS (m/z)

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

実験手順: At ice-bath temperature, lithium aluminium hydride (1.6 g, 42.16 mmol) was added in portions to a stirring mixture of (S)-2-benzyl piperazine-3,6-dione (3.0 g, 14.70 mmol) and tetrahydrofuran (80 ml). After 30 min at ice-bath temperature, the mixture was refluxed for 4 h with stirring. The reaction was quenched by the portionwise addition of sodium sulfate decahydrate and some methanol until hydrogen evolution ceased. It was filtered and the solids were washed several times with dichloromethane. The combined filtrates were evaporated to leave a white solid. MS (m/z): 177.1 (M+H)+; C11H16N2 requir. 176.3. the mixture was refluxed for 4 h The reaction was quenched by the portionwise addition of sodium sulfate decahydrate It was filtered the solids were washed several times with dichloromethane The combined filtrates were evaporated to leave a white solid

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

実験手順: At ice-bath temperature, lithium aluminium hydride (1.6 g, 42.16 mmol) was added in portions to a stirring mixture of (S)-2-benzyl piperazine-3,6-dione (3.0 g, 14.70 mmol) and tetrahydrofuran (80 ml). After 30 min at ice-bath temperature, the mixture was refluxed for 4 h with stirring. The reaction was quenched by the portionwise addition of sodium sulfate decahydrate and some methanol until hydrogen evolution ceased. It was filtered and the solids were washed several times with dichloromethane. The combined filtrates were evaporated to leave a white solid. MS (m/z): 177.1 (M+H)+; C11H16N2 requir. 176.3. the mixture was refluxed for 4 h The reaction was quenched by the portionwise addition of sodium sulfate decahydrate It was filtered the solids were washed several times with dichloromethane The combined filtrates were evaporated to leave a white solid

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

実験手順: A solution of 23.30 g (62.91 mmol) N-Benzyloxycarbonyl-phenylalanine-glycine-methylester (obtained above) in 650 ml dry methanol was hydrogenated by adding Pd/C-catalyst and stirring the resulting mixture under H2 at r.t. for 3 h. After that, the mixture was filtered through celite and then half of the solvent was evaporated. The remaining solution was refluxed for 17 h. Filtration of the white precipitate and washing it twice with methanol yielded 10.71 g (52.45 mmol, 83.37%) 6-(S)-Benzyl-piperazine-2,5-dione as a white solid. After that, the mixture was filtered through celite half of the solvent was evaporated The remaining solution was refluxed for 17 h Filtration of the white precipitate washing it twice with methanol

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

実験手順: A solution of 23.30 g (62.91 mmol) N-Benzyloxycarbonyl-phenylalanine-glycine-methylester (obtained above) in 650 ml dry methanol was hydrogenated by adding Pd/C-catalyst and stirring the resulting mixture under H2 at r.t. for 3 h. After that, the mixture was filtered through celite and then half of the solvent was evaporated. The remaining solution was refluxed for 17 h. Filtration of the white precipitate and washing it twice with methanol yielded 10.71 g (52.45 mmol, 83.37%) 6-(S)-Benzyl-piperazine-2,5-dione as a white solid. After that, the mixture was filtered through celite half of the solvent was evaporated The remaining solution was refluxed for 17 h Filtration of the white precipitate washing it twice with methanol

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

実験手順: At ice-bath temperature, lithium aluminium hydride (1.6 g, 42.16 mmol) was added in portions to a stirring mixture of (S)-2-benzylpiperazine-3,6-dione (3.0 g, 14.70 mmol) (comm. avail.) and tetrahydrofuran (80 ml). After 30 min at ice-bath temperature, the mixture was refluxed for 4 h with stirring. The reaction was quenched by the portionwise addition of sodium sulfate decahydrate and some methanol until hydrogen evolution ceased. It was filtered and the solids were washed several times with dichloromethane. The combined filtrates were evaporated to leave a white solid.MS (m/z): 177.1 (M+H)+; C11H16N2 requir. 176.3. the mixture was refluxed for 4 h The reaction was quenched by the portionwise addition of sodium sulfate decahydrate It was filtered the solids were washed several times with dichloromethane The combined filtrates were evaporated to leave a white solid.MS (m/z)