反应详情

温度

-3 °C

The solution of Vilsmeier reagent was prepared from dry N,N-dimethylformamide (0.4 g), phosphoryl chloride (0.8 ) and dry ethyl acetate (1.6 ml) in a usual manner. To the solution were added dry tetrahydrofuran (18 ml) and 2-(2-cyclopenten-1-yl)oxyimino-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (1.2 g) and then stirred at -3° to 3° C. (Solution A). A mixture of 7-amino-3-(tetrazolo[1,5-b]pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acid (1.5 g), sodium carbonate (0.9 g) and water (9.0 ml) was stirred to give a homogeneous solution. After the addition of acetone (9.0 ml), the solution was cooled to -3° C. and then thereto was added Solution A over a period of 5 minutes, keeping the temperature at -3° to 3° C. and the pH at 7.5 to 8.5 with triethyl amine. The resulting mixture was stirred for 30 minutes at the same temperature and pH. To the reaction mixture were added water, ethyl acetate and tetrahydrofuran. The resulting mixture was adjusted to pH 2.0 with 10% hydrochloric acid and filtered. The organic layer was separated from the filtrate, washed with water (×3), dried over magnesium sulfate, treated with activated charcoal and then evaporated. The residue was pulverized in isopropyl ether. The powder was collected by filtration, washed with isopropyl ether and then dried to give 7-[2-(2-cyclopenten-1-yl)oxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(tetrazolo[1,5-b]pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer)(1.83 g).

1. customto give a homogeneous solution
2. customat -3° to 3° C.
3. stirringThe resulting mixture was stirred for 30 minutes at the same temperature and pH
4. filtrationfiltered
5. customThe organic layer was separated from the filtrate
6. washwashed with water (×3)
7. dry with materialdried over magnesium sulfate
8. additiontreated with activated charcoal
9. customevaporated
10. filtrationThe powder was collected by filtration
11. washwashed with isopropyl ether
12. customdried