反应详情

温度

35 °C

Under nitrogen atmosphere, to a suspension of diphenylmethyl 7β-amino-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (30.2 g) in THF (800 ml) was added herein 1,3-bis(trimethylsilyl)urea (25.8 g) was added at the room temperature. The reaction mixture was warmed at 35° C. and dissolved, and then it was cooled below 0° C. A suspension of 2-(2-aminothiazol-4-yl)-2-(Z)-(acetoxyimino)acetylchloride monohydrochiloride salt (17.93 g) in acetonitrile (200 ml) was dropped into the above reaction mixture below 0° C. After stirring at the same temperature for 10 minutes, it was poured into a mixture of ethyl acetate (1.2 l) and ice-water (1.5 l). The aqueous layer was adjusted at pH 6.5 with saturated sodium bicarbonate solution. The organic layer was separated, washed with brine (1.0 l), and dried over magnesium sulfate, and then evaporated until the volume amounted to 500 ml. The solution was poured into IPE (1.5 l). The resulting precipitate was filtered, dried under reduced pressure to give diphenylmethyl 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(acetoxyimino)acetamido]-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (41.3 g) as powder.

1. additionwas added at the room temperature
2. dissolutiondissolved
3. temperatureit was cooled below 0° C
4. additionwas dropped into the above reaction mixture below 0° C
5. customThe organic layer was separated
6. washwashed with brine (1.0 l)
7. dry with materialdried over magnesium sulfate
8. customevaporated until the volume
9. additionThe solution was poured into IPE (1.5 l)
10. filtrationThe resulting precipitate was filtered
11. customdried under reduced pressure