* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Example 1 Production of (2S,5R)-5-benzyloxyamino-piperidine-2-carboxylic acid benzyl ester oxalate To the above product (0.946 g, 2.78 mmol), ethyl acetate was added to adjust the total weight at 8.63 g. The obtained mixture was heated up to 60°C, and methanol solution (0.875 g) containing oxalic acid (0.228 g, 2.53 mmol) was added for 5 minutes. The obtained reaction mixture was cooled down to room temperature, and the precipitate was filtrated. The precipitate was washed with ethyl acetate (2 ml) for 3 times, and dried under reduced pressure to obtain (2S,5R)-5-benzyloxyamino-piperidine-2-carboxylic acid benzyl ester oxalate (0.903 g, 2.10 mmol, yield: 76percent). The diastereo ratio of this solid was (2S,5R)/(2S,5S)=99.3/0.7 (98.6 percent de). To the above solid (0.597 g), methanol (3.0 g) was added, and the obtained mixture was stirred for 1 hour at 60°C. The reaction mixture was cooled down to room temperature, and the precipitate was filtrated. The precipitate was washed with methanol (2 ml) for 2 times, and dried under reduced pressure to obtain (2S,5R)-5-benzyloxyamino-piperidine-2-carboxylic acid benzyl ester oxalate (0.542 g). The diastereo ratio of this solid was (2S,5R)/(2S,5S)=99.93/0.07 (99.9 percent de).
Example 1 Production of (2S,5R)-5-benzyloxyamino-piperidine-2-carboxylic acid benzyl ester oxalate To the above product (0.946 g, 2.78 mmol), ethyl acetate was added to adjust the total weight at 8.63 g. The obtained mixture was heated up to 60C, and methanol solution (0.875 g) containing oxalic acid (0.228 g, 2.53 mmol) was added for 5 minutes. The obtained reaction mixture was cooled down to room temperature, and the precipitate was filtrated. The precipitate was washed with ethyl acetate (2 ml) for 3 times, and dried under reduced pressure to obtain (2S,5R)-5-benzyloxyamino-piperidine-2-carboxylic acid benzyl ester oxalate (0.903 g, 2.10 mmol, yield: 76%). The diastereo ratio of this solid was (2S,5R)/(2S,5S)=99.3/0.7 (98.6 %de). To the above solid (0.597 g), methanol (3.0 g) was added, and the obtained mixture was stirred for 1 hour at 60C. The reaction mixture was cooled down to room temperature, and the precipitate was filtrated. The precipitate was washed with methanol (2 ml) for 2 times, and dried under reduced pressure to obtain (2S,5R)-5-benzyloxyamino-piperidine-2-carboxylic acid benzyl ester oxalate (0.542 g). The diastereo ratio of this solid was (2S,5R)/(2S,5S)=99.93/0.07 (99.9 %de).
4-Amino-1-(benzyloxycarbonyl)piperidine (6.31 g, 26.9 mmol) and Ti(O-i-Pr)4 (7.61 g, 26.8 mmol) were added to tetrahydrofuran (30 mL), followed by stirring at 25C for 1 hour. To the reaction solution was added (2S,5R)-5-(benzyloxyamino)-piperidine-2-carboxyolic acid benzyl ester (7.57 g, 22.3 mmol), followed by stirring at 35C for 23 hours. Water (38 mL) and saturated aqueous sodium hydrogencarbonate solution (20 mL) were added in order, and the precipitated insoluble matter was filtered away. The filtrate was removed from aqueous layer, and the organic layer was washed with water (20 mL). The organic layer was concentrated to 31 g under reduced pressure, and hexane (50 mL) was added at 50C, followed by cooling to 0C. After stirring for 1 hour, precipitated solid was filtered out and then washed with hexane (40 mL), followed by drying at 40C under reduced pressure, to obtain the title compound (8.38 g, 81% yield).
With sodium hydrogencarbonate; In ethyl acetate; at 30 - 35℃; for 3h;
To stir,In a 500 ml four-necked flask with a thermometer, add 350 g of ethyl acetate.51.0 g (0.12 mol) of 5R-benzyloxy aminopiperidine-2S-carboxylic acid benzyl oxalate,100 g (0.24 mol) of 20% sodium bicarbonate solution,The reaction was stirred at 30-35C for 3 hours.The layers were separated and the aqueous layer was extracted twice with 100 grams each of ethyl acetate. Combine the organic layer and wash with saturated sodium chloride solutionPolyester twice, 50 grams each time. After the organic phase was recovered, the solvent was distilled off under reduced pressure to obtain a pale yellow viscous oil.5R-Benzyloxyaminopiperidine-2S-carboxylic acid benzyl ester, GC purity 99.6%, yield 96.5%.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
