反应详情

Phosphorus pentachloride (1.46 g, 7 mmoles) was added to a suspension of (Z)-2-(1-t-butoxycarbonylcyclobut-1-oxyimino)-2-(2-tritylaminothiazol-4-yl)acetic acid [IVe'] (4.09 g, 7 mmoles) in 70 mL of dry methylene chloride, and the mixture was stirred for 1 hour at room temperature. The acid chloride solution was added at -20° C. to a solution of silylated 7-ACA ester, which was prepared by adding BSA (5.6 mL, 21 mmoles) to a stirred suspension of benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochloride [V] (3.16 g, 7 mmoles) in dry methylene chloride (70 mL). The mixture was stirred for 20 minutes at -10° C. and then at room temperature for 40 minutes. The reaction mixture was evaporated and diluted with ethyl acetate (300 mL), and the organic layer was washed with 5% aqueous sodium bicarbonate, water and a saturated sodium chloride solution. After drying over sodium sulfate, the solvent was evaporated and the residue was purified by silica gel column chromatography (Wako gel C-200, 60 g); elution with chloroform. The fractions containing the desired product were combined and evaporated to obtain 5.88 g (86%) of VIe' as a yellow powder.

1. customwas prepared
2. additionby adding BSA (5.6 mL, 21 mmoles)
3. stirringThe mixture was stirred for 20 minutes at -10° C.
4. waitat room temperature for 40 minutes
5. customThe reaction mixture was evaporated
6. additiondiluted with ethyl acetate (300 mL)
7. washthe organic layer was washed with 5% aqueous sodium bicarbonate, water
8. dry with materialAfter drying over sodium sulfate
9. customthe solvent was evaporated
10. customthe residue was purified by silica gel column chromatography (Wako gel C-200, 60 g)
11. washelution with chloroform
12. additionThe fractions containing the desired product
13. customevaporated
14. customto obtain 5.88 g (86%) of VIe' as a yellow powder