反应详情

2.0 g (2.26 mmol) of Benzhydryl 3-chloromethyl-7-[(Z)-2-isopropoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylate 1-oxide was dissolved in 40 ml of acetone, and 750 mg (5 mmol) of sodium iodide was added thereto under cooling with ice. The mixture was stirred for 30 minutes. The reaction solution was concentrated under reduced pressure. To the residue, ethyl acetate and water were added. The organic layer was washed with a sodium metabisulfite aqueous solution and with a saturated sodium chloride aqueous solution, then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The oily residue was dissolved in 10 ml of N,N-dimethylformamide, and 790 mg (3.4 mmol) of 5,6-dihydroxyisoindoline hydrobromide was added thereto, then 0.47 ml (3.38 mmol) of triethylamine was dropwise added at room temperature. The reaction solution was stirred at the same temperature for 2 hours, and then N,N-dimethylformamide was distilled off under reduced pressure. To the residue, chloroform and water were added. The organic layer was washed with water and with a saturated sodium chloride aqueous solution, then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel flush column chromatography (5% methanol-chloroform) to obtain 1.74 g (yield: 78%) of the above-identified compound.

1. temperatureunder cooling with ice
2. concentrationThe reaction solution was concentrated under reduced pressure
3. additionTo the residue, ethyl acetate and water were added
4. washThe organic layer was washed with a sodium metabisulfite aqueous solution and with a saturated sodium chloride aqueous solution
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. dissolutionThe oily residue was dissolved in 10 ml of N,N-dimethylformamide
8. stirringThe reaction solution was stirred at the same temperature for 2 hours
9. distillationN,N-dimethylformamide was distilled off under reduced pressure
10. additionTo the residue, chloroform and water were added
11. washThe organic layer was washed with water and with a saturated sodium chloride aqueous solution
12. dry with materialdried over anhydrous sodium sulfate
13. concentrationconcentrated under reduced pressure
14. customThe residue was purified by silica gel
15. customflush column chromatography (5% methanol-chloroform)