反应详情

温度

0 °C

1 equivalent of 7-amino-3-[2-(3,4-dihydroxyphenyl)-1,3,4-thiadiazol-5-ylthiomethyl]ceph-3-em-4-carboxylic acid was silylated with 4 equivalents of bistrimethylsilylacetamide in anhydrous dichloromethane at room temperature for three hours. To this solution, cooled to 0° C. under argon, was added 1 equivalent of 2-[(Z)-ethoxyimino-2-(tritylaminothiazol-4-yl) acetic acid chloride (prepared from the corresponding acid (1 equivalent), 1 equivalent PCl5 and 1 equivalent TEA in dichloromethane at 0° C. for 2 hours followed by evaporation of the solvent and all POCl3, and redissolution in dichloromethane). After a few minutes at 0° C., the solvent was evaporated, and all the protecting groups removed by treating the crude reaction mixture with TFA/water for 1 hour at room temperature. The solvents were evaporated and the crude product dissolved in MeOH and precipitated in ether. Further purification was achieved by MPLC, to yield the title compound (7%), NMR (DMSOd6, AcOD, TFA), 1.25 (t,3H); 3.7 (m,2H); 4.2 and 4.25 (2d,2H); 4.4 (q,2H); 5.15 (d,1H); 5.75 (d,1H); 6.85 (d,1H); 7 (s,1H); 7.15 (d,1H); 7.3 (s,1H).

1. customfollowed by evaporation of the solvent
2. waitAfter a few minutes at 0° C.
3. customthe solvent was evaporated
4. customall the protecting groups removed
5. additionby treating the crude
6. customreaction mixture with TFA/water for 1 hour at room temperature
7. customThe solvents were evaporated
8. dissolutionthe crude product dissolved in MeOH
9. customprecipitated in ether
10. customFurther purification