Optically-active diazabicyclooctane derivative and method for manufacturing same

[0121] Among the compounds represented by the formula (F) of the present invention obtained by the above-mentioned production method of the present invention, the following formulas (F1), (F1-3a), (F1-3b), (F1-1a), (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazacyclo[3.2.1]octane-2- represented by (F1-2) and (F1-4) tert-butyl carboxylate, (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazacyclo[3.2.1]octane-2-carboxylate methyl ester, (2S,5R)-6-(Benzyloxy)-7-oxo-1,6-diazacyclo[3.2.1]octane-2-carboxylic acid allyl ester, (2S,5R)- Cyclohexylammonium salt of 6-(benzyloxy)-7-oxo-1,6-diazacyclo[3.2.1]octane-2-carboxylic acid, (2S,5R)-6-(benzyloxy base)-7-oxo-1,6-diazacyclo[3.2.1]octane-2-carboxylic acid and (2S,5R)-6-(benzyloxy)-7-oxo-1, 6-diazacyclo[3.2.1]octane-2-carboxamide can be obtained in the form of crystals of optically active diazacyclooctane derivatives, so it has the advantages of easy separation, purification, storage and transportation . This shows that the present invention is an indust...

[0413] (2S,5S)-5-Hydroxypiperidine-2-carboxylic acid tert-butyl ester (B)

[0414] [chemical formula 46]

[0415]

[0416] Add 10% palladium carbon ( moisture about 50%) 10.1 g, stirred vigorously at room temperature overnight under a hydrogen atmosphere. The catalyst mixture was filtered through celite, and the filtrate was concentrated to obtain 39.3 g of the title compound as a colorless solid (97% yield). The excess rate of optically active substances is above 99%ee (CHIRALPAK AD-H, 4.6×150mm, UV210nm, diethylamine / hexane / ethanol=0.1 / 80 / 20, flow rate 1mL / min, retention time 6.3min).

[0417] [α] 20 D -28.7°(c1.01, CHCl 3 ); 1 H NMR (400MHz, CDCl 3 ,δ):1.47(s,9H),1.63(m,1H),1.79-1.84(m,3H),2.82(dd,J=12.2,2.2Hz,1H),3.02(ddd,J=12.2,3.7 ,1.7Hz,1H),3.21(m,1H),3.80(m,1H);MS m / z:202(M+1).

[0419](2S,5S)-5-Hydroxy-1-(2,2,2-trifluoroacetyl)piperidine-2-carboxylic acid tert-butyl ester (C)

[0420] [chemical formula 47]

[0421]

[0422] Under argon atmosphere, the solution of 39.14 g (194 mmol) of (2S,5S)-5-hydroxypiperidine-2-carboxylic acid tert-butyl ester in anhydrous tetrahydrofuran (450 mL) was cooled to -3~-5 °C, and three 78.7 g (776 mmol) of ethylamine, and 81.5 g (388 mmol) of trifluoroacetic anhydride were added dropwise over 30 minutes. The reaction mixture was reacted at -3~-5°C for 1 hour, water (90 mL) was added, the temperature was raised to room temperature, and stirred for 1 hour. Water (740mL) was added to the reaction mixture, extracted with ethyl acetate (450mL×3 times), and the combined organic layer was sequentially washed with 5% aqueous citric acid (450mL), 6.5% aqueous sodium bicarbonate (450mL) and water ( 450mL) for washing. The residue obtained by distilling off the solvent under reduced pressure was subjected to silica gel colum...