【摘要】 本文研究了柠檬酸恩氯米芬的合成与表征。以N,N-二乙基乙醇胺、4-氟二苯甲酮为原料，叔丁醇钾、苄基氯化镁四氢呋喃溶液、氯化氢乙醇溶液、N-氯代丁二酰亚胺、联萘酚磷酸甲醇溶液等为反应试剂，经取代、消去、氯代等五步合成反应得到目标产物后，通过¹H NMR、¹³C NMR和ESI-MS表征其化学结构。中间产物（1）的最佳合成条件：叔丁醇钾190mmol，反应温度和时间分别为100℃、10h；中间产物（2）的最佳合成条件：2.0mol·L^-1苄基氯化镁四氢呋喃溶液95m L，反应温度和时间分别为20℃、24h；中间产物（3）的最佳合成条件：4.0mol·L^-1氯化氢乙醇溶液100m L，反应温度和时间分别为50℃、3h；中间产物（4）的最佳合成条件：N-氯代丁二酰亚胺85mmol，反应温度和时间分别为25℃、24h；随后选择40m L质量分数为40%的联萘酚磷酸甲醇溶液拆分Z/E构型，产物最终收率可达65.2%。经¹H NMR、¹³C NMR和ESI-MS表征，确认最终产物为柠檬酸恩氯米芬。更多还原

【Abstract】 The synthesis and characterization of trans-clomiphene citrate was investigated.The target compound was obtained by five step synthetic reaction that was substitution reaction,elimination reaction,chlorination reaction,and so on,using N,N-diethylethanolamine and 4-fluorobenzophenone as raw materials,potassium tertbutoxide,tetrahydrofuran solution of benzyl magnesium chloride,ethanol solution of hydrogen chloride,N-chlorosuccinimide,methanol solution of binaphthol phosphate as reaction reagent.The structure of the target compound was characterized by ¹H NMR,¹³C NMR and ESI-MS.The optimal reaction conditions of intermediate compound（1）were as follows:the dosage of potassium tert-butoxide was 190mmol,temperature and time of reaction were 100℃ and 10h,respectively.The optimal reaction conditions of intermediate compound（2）were as follows:the volume of 2.0mol·L^-1tetrahydrofuran solution of benzyl magnesium chloride was 95mL,temperature and time of reaction were 20℃ and 24h,respectively.The optimal reaction conditions of intermediate compound （3）were as follows:the volume of 4.0mol·L^-1ethanol solution of hydrogen chloride was 100mL,temperature and time of reaction were 50℃and 3h,respectively.The optimal reaction conditions of intermediate compound （4）were as follows:the dosage of N-chlorosuccinimide was 85mmol,temperature and time of reaction were 25℃ and 24h,respectively.The 40mL of methanol solution of binaphthol phosphate that mass concentration was 40% was selected for resolution of Z/E,and the ultimate yield was up to 65.2%.The ultimate product was verified by¹H NMR,¹³C NMR and ESI-MS,which was trans-clomiphene citrate.更多还原