反应详情

In a mixed solvent consisting of 200 ml of methylene chloride and 70 ml of methanol was dissolved 13.2 g of (3R,5R,6R)-6-amino-3-(3-benzylideneamino-2-oxoimidazolidin-1-yl)-3-(p-nitrobenzyloxycarbonyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane. Thereto were added 10.3 g of 2,4-dinitrophenylhydrazine and 9.83 g of p-toluenesulfonic acid monohydrate in this order. The mixture was stirred at room temperature for 1.5 hours. The insolubles were removed by filtration. The insolubles were washed with a mixed solvent consisting of 60 ml of methylene chloride and 20 ml of methanol. The washings and the filtrate obtained previously were combined, and mixed with 50 ml of water. The aqueous layer was separated. The organic layer was mixed with 30 ml of water and adjusted to pH 1.2 with 6N hydrochloric acid. The aqueous layer was separated. This aqueous layer and the aqueous layer obtained previously were combined and adjusted to pH 7 with sodium hydrogencarbonate. Thereto was added sodium chloride to saturation. Then, the aqueous layer was extracted with 150 ml of methylene chloride. The aqueous layer was further extracted 7 times each with 50 ml of methylene chloride. The extracts were combined with the organic layer obtained previously, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography (eluant: chloroform/methanol=50/1 to 15/1) to obtain 8.93 g (yield: 81.8%) of (3R, 5R,6R)-6-amino-3-(3-amino-2-oxoimidazolidin-1-yl)-3-(p-nitrobenzyloxycarbonyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane.

1. customThe insolubles were removed by filtration
2. washThe insolubles were washed with a mixed solvent
3. customThe washings and the filtrate obtained previously
4. customThe aqueous layer was separated
5. additionThe organic layer was mixed with 30 ml of water
6. customThe aqueous layer was separated
7. customThis aqueous layer and the aqueous layer obtained previously
8. extractionThen, the aqueous layer was extracted with 150 ml of methylene chloride
9. extractionThe aqueous layer was further extracted 7 times each with 50 ml of methylene chloride
10. customobtained previously
11. dry with materialdried over anhydrous magnesium sulfate
12. customThe solvent was removed by distillation under reduced pressure
13. customThe residue was purified by column chromatography (eluant: chloroform/methanol=50/1 to 15/1)