反应详情

To a stirred suspension of 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetic acid (III-1), (2.1 g, 10 mmole) in dry CH2Cl2 (50 ml) was added PCl5 (2.09 g, 10 mmole) at -30° C., and the mixture was stirred for 20 minutes at -15° to -20° C. To the above acid chloride solution was added a solution of diphenylmethyl 7-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochloride (II) (4.5 g, 10 mmole) in CH2Cl2 (50 ml) containing N,O-bis-(trimethylsilyl)acetamide (10 g, 50 mmole) at -30° C. After stirring at -10° C. for 1 hour, the mixture was concentrated to remove the CH2Cl2 and diluted with ethyl acetate (200 ml). The mixture was washed with 10% aqueous NaHCO3 (2×40 ml), H2O (2×20 ml) and brine (10 ml), successively, and dried over MgSO4. The solvent was evaporated in vacuo and the resulting oily residue (10 g) was dissolved in CHCl3 (20 ml) and chromatographed on a silica gel (Wako gel C-200, 100 g containing 10 ml of 1/1.5M pH 7 phosphate buffer) using 1-3% CH3OH--CHCl3. Fractions containing the title compound were evaporated to give 5.7 g (95%) of IV-1 as a yellow amorphous powder. M.p. >140° C. (dec.).

1. stirringAfter stirring at -10° C. for 1 hour
2. concentrationthe mixture was concentrated
3. customto remove the CH2Cl2
4. additiondiluted with ethyl acetate (200 ml)
5. washThe mixture was washed with 10% aqueous NaHCO3 (2×40 ml), H2O (2×20 ml) and brine (10 ml)
6. dry with materialsuccessively, and dried over MgSO4
7. customThe solvent was evaporated in vacuo
8. dissolutionthe resulting oily residue (10 g) was dissolved in CHCl3 (20 ml)
9. customchromatographed on a silica gel (Wako gel C-200, 100 g containing 10 ml of 1/1.5M pH 7 phosphate buffer)
10. additionFractions containing the title compound
11. customwere evaporated
12. customto give 5.7 g (95%) of IV-1 as a yellow amorphous powder