1-benzyl-4-hydroxypiperidine-4-carbonitrile;hydrochloride

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Conc. sulfuric acid (12 ml) was added to an ethanol solution (50 ml) of 1-benzyl-4-cyano-4-hydroxypiperidine hydrochloride (10 g) and the resulting mixture was heated at 130° C. for 24 hours in a sealed tube. After concentration of the reaction mixture, ice water was added to the concentrate. The resulting mixture was added with an aqueous solution of sodium hydrogencarbonate. After adjusting the thus-obtained solution to pH 7.0, it was extracted with diethyl ether. The extract was washed with brine and then added with anhydrous sodium sulfate to dry the same. The solvent was distilled off to obtain the intended product (9.7 g). was extracted with diethyl ether The extract was washed with brine added with anhydrous sodium sulfate to dry the same The solvent was distilled off

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

実験手順: A mixed solution of 18 ml conc. sulfuric acid and 1.8 ml water was cooled to 0° C., and 5 g of 1-benzyl-4-hydroxy-4-piperidinecarbonitrile hydrochloride was added thereto little by little. A mixed solution of 25 ml conc. sulfuric acid and 2.5 ml water was added thereto, and stirred at room temperature for 2 hr. It was left overnight in a freezer. The reaction solution was poured onto ice, and 47 g of sodium hydroxide was added thereto little by little. It was extracted 3 times with a mixed solvent of tetrahydrofuran and ethyl acetate (1:1). The extract was washed with brine, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was evaporated and subjected to silica gel column chromatography to give 3.19 g of 1-benzyl-4-hydroxy-4-piperidine carboxamide. It was left overnight in a freezer was added It was extracted 3 times with a mixed solvent of tetrahydrofuran and ethyl acetate (1:1) The extract was washed with brine dried over anhydrous magnesium sulfate filtered The filtrate was evaporated

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

実験手順: A mixed solution of 18 ml conc. sulfuric acid and 1.8 ml water was cooled to 0° C., and 5 g of 1-benzyl-4-hydroxy-4-piperidinecarbonitrile hydrochloride was added thereto little by little. A mixed solution of 25 ml conc. sulfuric acid and 2.5 ml water was added thereto, and stirred at room temperature for 2 hr. It was left overnight in a freezer. The reaction solution was poured onto ice, and 47 g of sodium hydroxide was added thereto little by little. It was extracted 3 times with a mixed solvent of tetrahydrofuran and ethyl acetate (1:1). The extract was washed with brine, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was evaporated and subjected to silica gel column chromatography to give 3.19 g of 1-benzyl-4-hydroxy-4-piperidine carboxamide. It was left overnight in a freezer was added It was extracted 3 times with a mixed solvent of tetrahydrofuran and ethyl acetate (1:1) The extract was washed with brine dried over anhydrous magnesium sulfate filtered The filtrate was evaporated

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

実験手順: A mixed solution of 18 ml conc. sulfuric acid and 1.8 ml water was cooled to 0° C., and 5 g of 1-benzyl-4-hydroxy-4-piperidinecarbonitrile hydrochloride was added thereto little by little. A mixed solution of 25 ml conc. sulfuric acid and 2.5 ml water was added thereto, and stirred at room temperature for 2 hr. It was left overnight in a freezer. The reaction solution was poured onto ice, and 47 g of sodium hydroxide was added thereto little by little. It was extracted 3 times with a mixed solvent of tetrahydrofuran and ethyl acetate (1:1). The extract was washed with brine, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was evaporated and subjected to silica gel column chromatography to give 3.19 g of 1-benzyl-4-hydroxy-4-piperidine carboxamide. It was left overnight in a freezer was added It was extracted 3 times with a mixed solvent of tetrahydrofuran and ethyl acetate (1:1) The extract was washed with brine dried over anhydrous magnesium sulfate filtered The filtrate was evaporated

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Conc. sulfuric acid (12 ml) was added to an ethanol solution (50 ml) of 1-benzyl-4-cyano-4-hydroxypiperidine hydrochloride (10 g) and the resulting mixture was heated at 130° C. for 24 hours in a sealed tube. After concentration of the reaction mixture, ice water was added to the concentrate. The resulting mixture was added with an aqueous solution of sodium hydrogencarbonate. After adjusting the thus-obtained solution to pH 7.0, it was extracted with diethyl ether. The extract was washed with brine and then added with anhydrous sodium sulfate to dry the same. The solvent was distilled off to obtain the intended product (9.7 g). was extracted with diethyl ether The extract was washed with brine added with anhydrous sodium sulfate to dry the same The solvent was distilled off

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

実験手順: A mixed solution of 18 ml conc. sulfuric acid and 1.8 ml water was cooled to 0° C., and 5 g of 1-benzyl-4-hydroxy-4-piperidinecarbonitrile hydrochloride was added thereto little by little. A mixed solution of 25 ml conc. sulfuric acid and 2.5 ml water was added thereto, and stirred at room temperature for 2 hr. It was left overnight in a freezer. The reaction solution was poured onto ice, and 47 g of sodium hydroxide was added thereto little by little. It was extracted 3 times with a mixed solvent of tetrahydrofuran and ethyl acetate (1:1). The extract was washed with brine, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was evaporated and subjected to silica gel column chromatography to give 3.19 g of 1-benzyl-4-hydroxy-4-piperidine carboxamide. It was left overnight in a freezer was added It was extracted 3 times with a mixed solvent of tetrahydrofuran and ethyl acetate (1:1) The extract was washed with brine dried over anhydrous magnesium sulfate filtered The filtrate was evaporated