methyl 2-piperidin-2-ylacetate;hydrochloride

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

実験手順: In 13 ml of acetonitrile was dissolved 1.0 g (5.16 mol) of 2-carbomethoxymethylpiperidine hydrochloride, and 1.77 ml (12.72 mmol) of triethylamine and 0.76 ml (6.36 mmol) of benzyl bromide were added to the solution at room temperature, and the resulting mixture was reacted at the same temperature under stirring for 5 hours. After completion of the reaction, the obtained reaction mixture was filtered and then concentrated under reduced pressure, then, 25 ml of ethyl acetate and 15 ml of a saturated aqueous sodium hydrogen carbonate solution were added to the residue and the organic layer was extracted. The obtained organic layer was washed with 15 ml of a saturated aqueous sodium hydrogen carbonate solution, and saturated saline solution, dried over anhydrous magnesium sulfate, then, filtered and the filtrate was concentrated under reduced pressure to obtain 0.97 g of an oily substance. The resulting oily substance was purified by silica gel column chromatography (WAKOGEL C-200 (trade name), n-hexane/ethyl acetate=4/1(volume ratio)) to obtain 0.75 g (Isolated yield based on 2-carbomethoxymethylpiperidine hydrochloride=59%) of N-benzyl-2-carbomethoxymethylpiperidine. were added to the solution at room temperature the resulting mixture was reacted at the same temperature After completion of the reaction the obtained reaction mixture was filtered concentrated under reduced pressure 25 ml of ethyl acetate and 15 ml of a saturated aqueous sodium hydrogen carbonate solution were added to the residue the organic layer was extracted The obtained organic layer was washed with 15 ml of a saturated aqueous sodium hydrogen carbonate solution, and saturated saline solution dried over anhydrous magnesium sulfate filtered the filtrate was concentrated under reduced pressure to obtain 0.97 g of an oily substance The resulting oily substance was purified by silica gel column chromatography (WAKOGEL C-200 (trade name), n-hexane/ethyl acetate=4/1(volume ratio)) to obtain 0.75 g (Isolated yield based on 2-carbomethoxymethylpiperidine hydrochloride=59%) of N-benzyl-2-carbomethoxymethylpiperidine

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

実験手順: In 13 ml of acetonitrile was dissolved 1.0 g (5.16 mol) of 2-carbomethoxymethylpiperidine hydrochloride, and 1.77 ml (12.72 mmol) of triethylamine and 0.76 ml (6.36 mmol) of benzyl bromide were added to the solution at room temperature, and the resulting mixture was reacted at the same temperature under stirring for 5 hours. After completion of the reaction, the obtained reaction mixture was filtered and then concentrated under reduced pressure, then, 25 ml of ethyl acetate and 15 ml of a saturated aqueous sodium hydrogen carbonate solution were added to the residue and the organic layer was extracted. The obtained organic layer was washed with 15 ml of a saturated aqueous sodium hydrogen carbonate solution, and saturated saline solution, dried over anhydrous magnesium sulfate, then, filtered and the filtrate was concentrated under reduced pressure to obtain 0.97 g of an oily substance. The resulting oily substance was purified by silica gel column chromatography (WAKOGEL C-200 (trade name), n-hexane/ethyl acetate=4/1(volume ratio)) to obtain 0.75 g (Isolated yield based on 2-carbomethoxymethylpiperidine hydrochloride=59%) of N-benzyl-2-carbomethoxymethylpiperidine. were added to the solution at room temperature the resulting mixture was reacted at the same temperature After completion of the reaction the obtained reaction mixture was filtered concentrated under reduced pressure 25 ml of ethyl acetate and 15 ml of a saturated aqueous sodium hydrogen carbonate solution were added to the residue the organic layer was extracted The obtained organic layer was washed with 15 ml of a saturated aqueous sodium hydrogen carbonate solution, and saturated saline solution dried over anhydrous magnesium sulfate filtered the filtrate was concentrated under reduced pressure to obtain 0.97 g of an oily substance The resulting oily substance was purified by silica gel column chromatography (WAKOGEL C-200 (trade name), n-hexane/ethyl acetate=4/1(volume ratio)) to obtain 0.75 g (Isolated yield based on 2-carbomethoxymethylpiperidine hydrochloride=59%) of N-benzyl-2-carbomethoxymethylpiperidine

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

実験手順: In 13 ml of acetonitrile was dissolved 1.0 g (5.16 mol) of 2-carbomethoxymethylpiperidine hydrochloride, and 1.77 ml (12.72 mmol) of triethylamine and 0.76 ml (6.36 mmol) of benzyl bromide were added to the solution at room temperature, and the resulting mixture was reacted at the same temperature under stirring for 5 hours. After completion of the reaction, the obtained reaction mixture was filtered and then concentrated under reduced pressure, then, 25 ml of ethyl acetate and 15 ml of a saturated aqueous sodium hydrogen carbonate solution were added to the residue and the organic layer was extracted. The obtained organic layer was washed with 15 ml of a saturated aqueous sodium hydrogen carbonate solution, and saturated saline solution, dried over anhydrous magnesium sulfate, then, filtered and the filtrate was concentrated under reduced pressure to obtain 0.97 g of an oily substance. The resulting oily substance was purified by silica gel column chromatography (WAKOGEL C-200 (trade name), n-hexane/ethyl acetate=4/1(volume ratio)) to obtain 0.75 g (Isolated yield based on 2-carbomethoxymethylpiperidine hydrochloride=59%) of N-benzyl-2-carbomethoxymethylpiperidine. were added to the solution at room temperature the resulting mixture was reacted at the same temperature After completion of the reaction the obtained reaction mixture was filtered concentrated under reduced pressure 25 ml of ethyl acetate and 15 ml of a saturated aqueous sodium hydrogen carbonate solution were added to the residue the organic layer was extracted The obtained organic layer was washed with 15 ml of a saturated aqueous sodium hydrogen carbonate solution, and saturated saline solution dried over anhydrous magnesium sulfate filtered the filtrate was concentrated under reduced pressure to obtain 0.97 g of an oily substance The resulting oily substance was purified by silica gel column chromatography (WAKOGEL C-200 (trade name), n-hexane/ethyl acetate=4/1(volume ratio)) to obtain 0.75 g (Isolated yield based on 2-carbomethoxymethylpiperidine hydrochloride=59%) of N-benzyl-2-carbomethoxymethylpiperidine

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-(trifluoromethyl)benzenesulfonyl chloride (1 eq) in dichloromethane (1.6 ml/mmol) was added dropwise to a cooled solution (0° C.) of methyl 2-(piperidin-2-yl)acetate hydrochloride (1.1 eq) in dichloromethane (40 ml/mmol) and triethylamine (2.5 eq). The mixture was stirred for 90 min at 25° C., after which the reaction was completed (thin-layer chromatographic analysis). Hydrogen chloride solution (0.5 mol/l, 2 ml/mmol) was added and the mixture was stirred for 15 min. The organic phase was separated off, washed with water, dried over sodium sulfate and concentrated to small volume under vacuum. Yield: 80% the mixture was stirred for 15 min The organic phase was separated off washed with water dried over sodium sulfate concentrated to small volume under vacuum

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

実験手順: Thionyl chloride (5.5 ml, 75 mmol) was added to a solution of 2-carboxymethylpiperidine-1-carboxylic acid tert-butyl ester (6 g, 25 mmol) in methanol (60 ml) while stirring and the mixture was then refluxed for 16 h. The solvent was removed under vacuum and the crude product used in the next stage without purification. Yield: 90% the mixture was then refluxed for 16 h The solvent was removed under vacuum the crude product used in the next stage without purification

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

実験手順: A solution of 3,4-dichlorobenzenesulfonyl chloride (1.88 g, 7.65 mmol) in DCM (15 ml) was added at 0° C. to a solution, cooled to 0° C., of piperidin-2-ylacetic acid methyl ester hydrochloride (1.3 g, 8.4 mmol) in DCM (33 ml) and triethylamine (2.66 ml, 21 mmol), and stirring was then carried out for 90 minutes at room temperature. 0.5 M HCl (20 ml) was then added, and stirring was carried out for a further 15 minutes. The organic phase was separated off, washed with water and dried over sodium sulfate. The solvent was removed using a rotary evaporator and the product was used in the next stage without being purified further. Yield: 1.9 g (63%) stirring was carried out for a further 15 minutes The organic phase was separated off washed with water dried over sodium sulfate The solvent was removed a rotary evaporator without being purified further

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

実験手順: Thionyl chloride (1.8 ml, 25.2 mmol) was added dropwise to a solution, cooled to 0° C., of piperidin-2-ylacetic acid hydrochloride (1.5 g, 8.4 mmol) in methanol (35 ml), and the mixture was heated for 16 h at gentle boiling and then cooled to room temperature. The solvent was removed azeotropically in vacuo with benzene. Yield: 1.3 g (100%) the mixture was heated for 16 h at gentle boiling The solvent was removed azeotropically in vacuo with benzene

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

実験手順: In 13 ml of acetonitrile was dissolved 1.0 g (5.16 mol) of 2-carbomethoxymethylpiperidine hydrochloride, and 1.77 ml (12.72 mmol) of triethylamine and 0.76 ml (6.36 mmol) of benzyl bromide were added to the solution at room temperature, and the resulting mixture was reacted at the same temperature under stirring for 5 hours. After completion of the reaction, the obtained reaction mixture was filtered and then concentrated under reduced pressure, then, 25 ml of ethyl acetate and 15 ml of a saturated aqueous sodium hydrogen carbonate solution were added to the residue and the organic layer was extracted. The obtained organic layer was washed with 15 ml of a saturated aqueous sodium hydrogen carbonate solution, and saturated saline solution, dried over anhydrous magnesium sulfate, then, filtered and the filtrate was concentrated under reduced pressure to obtain 0.97 g of an oily substance. The resulting oily substance was purified by silica gel column chromatography (WAKOGEL C-200 (trade name), n-hexane/ethyl acetate=4/1(volume ratio)) to obtain 0.75 g (Isolated yield based on 2-carbomethoxymethylpiperidine hydrochloride=59%) of N-benzyl-2-carbomethoxymethylpiperidine. were added to the solution at room temperature the resulting mixture was reacted at the same temperature After completion of the reaction the obtained reaction mixture was filtered concentrated under reduced pressure 25 ml of ethyl acetate and 15 ml of a saturated aqueous sodium hydrogen carbonate solution were added to the residue the organic layer was extracted The obtained organic layer was washed with 15 ml of a saturated aqueous sodium hydrogen carbonate solution, and saturated saline solution dried over anhydrous magnesium sulfate filtered the filtrate was concentrated under reduced pressure to obtain 0.97 g of an oily substance The resulting oily substance was purified by silica gel column chromatography (WAKOGEL C-200 (trade name), n-hexane/ethyl acetate=4/1(volume ratio)) to obtain 0.75 g (Isolated yield based on 2-carbomethoxymethylpiperidine hydrochloride=59%) of N-benzyl-2-carbomethoxymethylpiperidine