Improvement of Synthetic Technology of Nateglinide / 中国药房

ABSTRACT

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 phosphorus trichloride or phosphorus pentachloride was substituted by thionyl chloride for the chlorination,and PtO2 or Raney Ni was substituted by RuNiAlC 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.RESULTS: The crystal form characterization results demonstrated that the product was H form crystal and its yield reached 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.