选择性胆固醇吸收抑制剂-依泽替米贝的合成工艺改进

Selective Inhibitor of Cholesterol Absorption-an Improved Process for the Synthesis of Ezetimibe

化合物7与1,3-丙二醇反应生成化合物8,与新戊酰氯和S-(+)-4-苯基-2-噁唑烷酮反应生成化合物9,然后在钛化合物催化的条件下与化合物4反应生成化合物10,再成环生成具有β-内酰胺的化合物11,最后经CBS手性还原剂还原得到依泽替米贝。并通过质谱、核磁共振氢谱和碳谱对目标产物进行了结构表征。该合成路线短,反应条件温和,工艺操作简单,成本较低,收率和纯度较高,适合工业化生产。

Starting with N-（5-（（diphenylphosphoryl）methyl）-4-（4-fluorophenyl）-6-isopropylpyrimidin-2-yl）-N-methylmethanesulfonamide（C28H29FN3O3PS）,rosuvastatin calcium was prepared through condensation,hydrolysis and deprotection,esterification,hydrolysis,salting.The process was redesigned and the optimum technological conditions were investigated.Thus,the total yield reached 34.3 %,HPLC purity 99 %.The Structure was determined by MS,CNMR and HNMR.The process exhibits simple,cost-efficient,high purity and yield,easy to scale up.