【摘要】 目的 合成盐酸度洛西汀。方法 以2-乙酰基噻吩、盐酸二甲胺和多聚甲醛为起始原料，经Mannich反应、硼氢化钠还原、手性拆分、成醚、单甲基化、成盐、两次重结晶等七步制得抗抑郁药盐酸度洛西汀，并对原工艺进行了改进。结果及结论 目标化合物的总收率为：24.1%，结构经质谱、核磁共振氢谱及元素分析等确证，纯度可达99%，本路线反应条件温和，原料来源方便，成本低，并经中试验其收率仍在24%左右，说明可以进行工业化生产。

    【关键词】 药物化学；制备；化学合成； 度洛西汀

    An improved synthesis method of duloxetine hydrochloride

    SHAO Qiu-rong,WU Jin-chang.Shunde Entry-Exit Inspection and Quarantine Bureau Agricultural and Chemical Products Laboratory,Shunde 528303,China

    【Abstract】 Objective To synthesis duloxetine hydrochloride.Methods The synthesis started from commercially available of 2-acetylthiophene by a sequence of reactions including Mannich reaction, reduction by sodium borohydride, resolution with L-(+)-mandelic acid, etherification with 1-fluoronaphthalene,methylation , salt formation with hydrochloric acid /ether, dual crystallatios.Results The final product was fully characterized by HPLC-MS,1HNMR,element analysis,IR,UV and DTA. The overall yield was 24.1% in hundreds grams scale.Conclusion This approach is more applicable for industrial production compared with the reported method. ......