Optimizing Synthesis Process Of A New Triazole Antifungal Agent: Voriconazole

Voriconazole, a new triazole antifungal agent, was researched by Pfizer Co., and was sold at first in American market in 2002. As one of fluconazole derivatives, It is mainly used for treating the acute or chronic deep fungal infection on clinic. Because it has the characteristics of broad spectrum antifungal, strong antifungal efficiency and good security, this product will occupy the great civil market with the demand of antifungal agent increasing rapidly. It will be worth of optimizing the process for synthesis of voriconazole so that it more suit large-scale production and improve economic benefit.In this thesis, large number of related literatures was summarized, and the process for the preparation of voriconazole was also detailed analyzed. Following the reported method, we studied the synthetic route of voriconazole and successfully prepared the voriconazole with lower material cost. The route includes: mucleophilic substitution, chloric substitution, bromic substitution, condensation and hydrogenation etc. The intermediates and voriconazole was identified by HPLC and 1H-NMR.Under triethylamine as the phase transfer catalyzer and sodium hydroxide as the alkalescent catalyzer, with ethyl fluoroacetate reacting to propionyl chloride, not only the reaction condition was mildness but also the yield was higher too. The key factors influencing the mucleophilic substitution in this reaction system were studied. Finally, the optimal process condition was obtained. We analyzed 2-ethly fluoropropionylacetate with a new means: HPLC. We can acquire the exact results...