那格列奈合成工艺改进

Improvement of Synthetic Technology of Nateglinide

目的:改进那格列奈的合成工艺以提高产率并促进工业化生产。方法:分别从反应试剂、催化剂及晶型转型方面进行改进,即在顺反转化中用氢氧化钠替代文献中的氢化钠,在氯化反应中用氯化亚砜代替文献中的三氯化磷或五氯化磷;以RuNiAlC催化剂代替文献中的PtO2或Raney Ni;在H晶型转型中采用低温粉碎得微粒晶种以晶种引导结晶的方法获得H型晶体,并对改进方法所制成品的晶型结构进行表征及计算产率。结果:晶型表征结果证实产品为那格列奈H型晶体,产率达72%,高于文献报道的50%。结论:改进后工艺的产率升高,适合工业化生产。

OBJECTIVE： To improve the synthetic technology of nateglinide so as to increase yield and promote industrial production. METHODS： The improvement was conducted from aspects of reagent, catalyst, crystal form transformation etc in which the sodium hydride reported in literature was substituted by sodium hydrate in cis - trans transformation, and phos- phorus trichloride or phosphorus pentachloride was substituted by thionyl chloride for the chlorination, and PtO2 or Raney Ni was substituted by RuNiA1C as catalytic agent. In H form crystal form transformation, fine seed - crystal was obtained by low temperature crushing, which was added with seed- crystal to induce crystallization to obtain H form crystal. The structure of the crystal form of the product obtained using the improved technology was characterized and its yield was computed. RE- SULTS： The crystal form characterization results demonstrated that the product was H form crystal and its yield reaehed 72%, higher than that reported in literature （50%） . CONCLUSION： The improved technology of nateglinide contributed to the increase of its yield; Therefore, this technology is suitable for industrial production.