盐酸度洛西汀的合成工艺改进
n Improved Synthesis Method of Duloxetine Hydrochlorid
目的 本文针对药物盐酸度洛西汀的合成工艺，提出了改进的措施，确立了最佳反应条件，合成了盐酸度洛西汀。方法 以2-乙酰噻吩、二甲胺盐酸盐和多聚甲醛为起始原料，经Mannnich反应、还原、拆分、拆分、醚化、脱甲基、成盐等反应制得盐酸度洛西汀。对拆分后剩余液中的R构型的N,N-二甲基-3-羟基-（2-噻吩基）-丙胺进行了消旋再拆分，这是主要进行的工艺改进，很适合工业上的再利用理念。另外更换了部分反应试剂，使得反应收率进一步提高。结果 所得目标化合物的结构经质谱、核磁共振氢谱以及红外光谱确证,总收率由文献报道的21%提高到32%。结论 该工艺可降低成本，操作简化，收率高，适合工业化生产。
Objective: To synthesize duloxetine hydrochloride and optimize the process，achieve optimized conditions. Methods Duloxetine hydrochloride was synthesized by steps of reaction Mannich reachtion, reduction, separation, ethrication, demethylation and salification from 2-acetylthiophene plus dimethylamine hydrochloride and paraformaldehyde. Key study focused on racemization of the intermediate (R)-(+)-N,N-dimethyl-3-hydroxy-3-(2-thienyl)propanamine. The racemic product can be reused in the synthesis of duloxetine. Moreover some reagents reported in literature were changed. Results the structure of duloxetine was elucidated by MS，1H-NMR and IR. The overall yield was 32% higther than that reported in literature21%. Conclusion The method is of low cost and of high yield, facile and suitable for industry.
赵姣、刘敏、章文军
药学制药化学工业
盐酸度洛西汀合成消旋再拆分收率
uloxetine hydrochlorideSynthesisRacemization of the intermediateYield
赵姣,刘敏,章文军.盐酸度洛西汀的合成工艺改进[EB/OL].(2008-12-18)[2025-08-16].http://www.paper.edu.cn/releasepaper/content/200812-572.点此复制
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