(3R)-3-[(2-甲基丙-2-基)氧基甲基]哌嗪-2-one

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution that was prepared by dissolving 100.0 g of (R)-3-(t-butoxymethyl)piperazine-2-one to 500 mL of acetone, and then by dissolving 207.4 g of di-p-toluoyl-L-tartaric acid to 700 mL of acetone was slowly added to a reactor. The resulting reaction solution was stirred for 1 hour, and then resulting solid was filtered to obtain 251.4 g of a title compound. A solution that was prepared was slowly added to a reactor The resulting reaction solution resulting solid was filtered

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 39.5 kg of (R)-methyl 2-(2-(benzyloxycarbonylamino)ethylamino)-3-t-butoxypropanoate was dissolved in 276 L of methanol in a reactor; purged with nitrogen; 5.9 kg of palladium/carbon (10% water mixture) was added and stirred for 3 hours while the hydrogen pressure was maintained at 10 bar. The reaction solution was filtered, concentrated under reduced pressure, and then again azeotroped by adding 30 L of isopropylether. 158 L (115 kg) of isopropylether, 39 L (35 kg) of ethyl acetate, and 36.4 kg of silica gel were added to a concentrated solution, stirred for 1 hour, decompression-filtered, and then concentrated under reduced pressure. A concentrated residue was azeotroped by adding 30 L of methanol, and then a concentrated solution and 221 L of methanol were added to a reactor. After purging with nitrogen, 11.85 kg of palladium/carbon (10% water mixture) was added, and then stirred for 6 hours while hydrogen pressure was maintained at 15 bar. The reaction solution was filtered, and then concentrated under reduced pressure. An aqueous layer was isolated in twice by adding 80 L of isopropylether and 80 L of purified water to the concentrated solution. An organic layer was isolated after adding methylene chloride/isopropanol=5:1 (126 L) to the aqueous layer and then stirring in 5 times. The organic layer was dehydration-filtered with 50 kg of sodium sulfate to obtain 9.7 kg of a title compound. purged with nitrogen 5.9 kg of palladium/carbon (10% water mixture) was added was maintained at 10 bar The reaction solution was filtered concentrated under reduced pressure again azeotroped by adding 30 L of isopropylether 158 L (115 kg) of isopropylether, 39 L (35 kg) of ethyl acetate, and 36.4 kg of silica gel were added to a concentrated solution stirred for 1 hour decompression-filtered concentrated under reduced pressure A concentrated residue was azeotroped by adding 30 L of methanol a concentrated solution and 221 L of methanol were added to a reactor After purging with nitrogen, 11.85 kg of palladium/carbon (10% water mixture) was added stirred for 6 hours while hydrogen pressure was maintained at 15 bar The reaction solution was filtered concentrated under reduced pressure An aqueous layer was isolated in twice An organic layer was isolated stirring in 5 times The organic layer was dehydration-filtered with 50 kg of sodium sulfate

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 10.0 g of (R)-3-t-butoxycarbonylamino-4-(2,4,5-trifluorophenyl)butanoic acid (Chemical Formula 2) produced in the above Example 1 was dissolved in 450 mL of toluene in 2 L flask; 13.0 g of bis(2,2′-benzothiazolyl)disulfide and 10.2 g of triphenylphosphine were added; and then the resulting reaction solution was cooled to 0° C. While stirring the reaction solution, a solution prepared by dissolving 0.8 mL of triethylamine to 20 mL of toluene was added, and then stirred for 5 hours at room temperature. The reaction solution was cooled to 0° C., and then a solution prepared by dissolving 5.6 g of (R)-3-(t-butoxymethyl)piperazine-2-one (Chemical Formula 3) produced in the above Example 2 to 40 mL of toluene, and 2.4 mL of pyridine were slowly added. After 30 minutes, the temperature of the reaction solution was increased to room temperature, and then stirred for further 1 hour. pH of the reaction solution was adjusted to 2.5 using saturated citric acid aqueous solution, and then diluted with 400 mL of ethyl acetate. The reaction solution was washed with brine in twice, and an organic layer was dehydration-concentrated with magnesium sulfate. A residue was purified with column chromatography to obtain 838 mg of a title compound. and then the resulting reaction solution a solution prepared was added stirred for 5 hours at room temperature The reaction solution was cooled to 0° C. a solution prepared were slowly added the temperature of the reaction solution was increased to room temperature stirred for further 1 hour The reaction solution was washed with brine in twice, and an organic layer was dehydration-concentrated with magnesium sulfate A residue was purified with column chromatography