tert-butyl 4-benzylpiperazine-1-carboxylate

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: To 1-benzyl-4-tert-butoxycarbonylpiperazine (3.12 g), saturated ethanol hydrochloride was added, followed by stirring for 90 minutes at room temperature. The solvent was distilled off under reduced pressure, followed by drying, whereby the title compound (2.73 g, 97%) was obtained as white powder. The solvent was distilled off under reduced pressure by drying

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

実験手順: In acetonitrile (80 ml), tert-butyl 1-piperazine carboxylate (2.50 g) was dissolved. Under ice cooling, benzyl bromide (1.59 ml) and triethylamine (1.87 ml) were added dropwise to the resulting solution, followed by stirring at room temperature for 90 minutes. After the solvent was distilled off under reduced pressure, distilled water and dichloromethane were added to the residue to separate the organic layer. The organic layer was washed with saturated aqueous NaCl solution and dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent under reduced pressure was purified by chromatography on a silica gel column (ethyl acetate:hexane=1:20 to 1:5), whereby the title compound (3.12 g, 84%) was obtained as colorless powder. After the solvent was distilled off under reduced pressure distilled water and dichloromethane were added to the residue to separate the organic layer The organic layer was washed with saturated aqueous NaCl solution dried over anhydrous sodium sulfate The residue obtained by distilling off the solvent under reduced pressure was purified by chromatography on a silica gel column (ethyl acetate:hexane=1:20 to 1:5), whereby the title compound (3.12 g, 84%) was obtained as colorless powder

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

実験手順: To 1-benzyl-4-tert-butoxycarbonylpiperazine (3.12 g), saturated ethanol hydrochloride was added, followed by stirring for 90 minutes at room temperature. The solvent was distilled off under reduced pressure, followed by drying, whereby the title compound (2.73 g, 97%) was obtained as white powder. The solvent was distilled off under reduced pressure by drying

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

実験手順: In acetonitrile (80 ml), tert-butyl 1-piperazine carboxylate (2.50 g) was dissolved. Under ice cooling, benzyl bromide (1.59 ml) and triethylamine (1.87 ml) were added dropwise to the resulting solution, followed by stirring at room temperature for 90 minutes. After the solvent was distilled off under reduced pressure, distilled water and dichloromethane were added to the residue to separate the organic layer. The organic layer was washed with saturated aqueous NaCl solution and dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent under reduced pressure was purified by chromatography on a silica gel column (ethyl acetate:hexane=1:20 to 1:5), whereby the title compound (3.12 g, 84%) was obtained as colorless powder. After the solvent was distilled off under reduced pressure distilled water and dichloromethane were added to the residue to separate the organic layer The organic layer was washed with saturated aqueous NaCl solution dried over anhydrous sodium sulfate The residue obtained by distilling off the solvent under reduced pressure was purified by chromatography on a silica gel column (ethyl acetate:hexane=1:20 to 1:5), whereby the title compound (3.12 g, 84%) was obtained as colorless powder

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-benzyl-piperazine-1-carboxylic acid tert-butyl ester (2 g) in diethylether (35 mL) was added tetramethylethylenediamine (1.4 mL). The resulting mixture was cooled to −70° C. and sec-butyllithium (7 mL of a 1.3 M solution) was added dropwise, after complete addition the solution was slowly warmed to −10° C., at which temperature the mixture was stirred for one hour. Subsequently, the mixture was recooled to −70° C.; then a solution of 2-(bromomethyl)naphthalene (2 g) in diethylether was added dropwise and stirring continued at −70° C. was continued for one hour. The resulting mixture was stirred and allowed to come to room temperature overnight, then partitioned between saturated ammonium chloride (aq) and ethyl acetate. The organic layer was dried over magnesium sulphate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (SiO2, CH2Cl2/MeOH 99/1) to afford 4-benzyl-2-(naphthalen-2-ylmethyl)piperazine-1-carboxylic acid tert-butyl ester as an oil. 0.8 g (27 %) Rf 0.47 (CH2Cl2/MeOH 99/1), MH+ 417. after complete addition the solution was slowly warmed to −10° C., at which temperature the mixture was recooled to −70° C. stirring continued at −70° C. was continued for one hour The resulting mixture was stirred to come to room temperature overnight partitioned between saturated ammonium chloride (aq) and ethyl acetate The organic layer was dried over magnesium sulphate filtered concentrated in vacuo The residue was purified by flash chromatography (SiO2, CH2Cl2/MeOH 99/1)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-benzyl-piperazine-1-carboxylic acid tert-butyl ester (2 g) in diethylether (35 mL) was added tetramethylethylenediamine (1.4 mL). The resulting mixture was cooled to −70° C. and sec-butyllithium (7 mL of a 1.3 M solution) was added dropwise, after complete addition the solution was slowly warmed to −10° C., at which temperature the mixture was stirred for one hour. Subsequently, the mixture was recooled to −70° C.; then a solution of 2-(bromomethyl)naphthalene (2 g) in diethylether was added dropwise and stirring continued at −70° C. was continued for one hour. The resulting mixture was stirred and allowed to come to room temperature overnight, then partitioned between saturated ammonium chloride (aq) and ethyl acetate. The organic layer was dried over magnesium sulphate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (SiO2, CH2Cl2/MeOH 99/1) to afford 4-benzyl-2-(naphthalen-2-ylmethyl)piperazine-1-carboxylic acid tert-butyl ester as an oil. 0.8 g (27 %) Rf 0.47 (CH2Cl2/MeOH 99/1), MH+ 417. after complete addition the solution was slowly warmed to −10° C., at which temperature the mixture was recooled to −70° C. stirring continued at −70° C. was continued for one hour The resulting mixture was stirred to come to room temperature overnight partitioned between saturated ammonium chloride (aq) and ethyl acetate The organic layer was dried over magnesium sulphate filtered concentrated in vacuo The residue was purified by flash chromatography (SiO2, CH2Cl2/MeOH 99/1)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,1-Dimethylethyl 4-(phenylmethyl)-1-piperazine carboxylate (20 g, 72 mmol) and tetramethylethylenediamine (18 g, 0.16 mol) were dissolved in tetrahydrofuran (100 mL), and the solution was cooled to −78° C. A 1.0 M solution of sec-butyllithium in hexane and cyclohexane (150 mL, 0.15 mol) was added thereto, and the mixture was stirred for 2 hours and the temperature was elevated to −30° C. After cooling to −78° C. again, a solution of benzophenone (28 g, 0.15 mol) in tetrahydrofuran (70 mL) was added dropwise thereto, and the mixture was stirred for 18 hours while elevating the temperature to room temperature. To the reaction solution was added an aqueous saturated ammonium chloride solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (hexane:ethyl acetate=3:1) to obtain the title compound (18 g, yield 64%) as crystals. was elevated to −30° C After cooling to −78° C. again the mixture was stirred for 18 hours to room temperature the resulting mixture was extracted with ethyl acetate The extract was washed with water concentrated under reduced pressure The residue was purified with silica gel column chromatography (hexane:ethyl acetate=3:1)