Synthesis and Technology Optimization of Dapoxetine Hydrochloride / 中国药房

ABSTRACT

OBJECTIVE：To optimize the synthesis process of dapoxetine hydrochloride. METHODS ：By chiral synthesis ， asymmetric reduction was carried out by using 3-chlorophenylacetone as raw material ，（1S，2R）-（-）-1-amino-2-indanol as catalyst，and borane- N，N-diethylaniline （DEANB） as reducing agent. Then ，it was reacted with α-naphthol etherification， sulfonation，dimethylamine substitution ，and HCl salt formation reaction to obtain the final products. The products were characterized by NMR and MS. The synthesis reaction of intermediate Ⅰ，intermediate Ⅱ，intermediate Ⅲ and the final product were optimized. RESULTS ：The final product was dapoxetine hydrochloride with purity of 99.8％ and yield of 58.9％. Compared with traditional splitting technology ，the chiral synthesis technology of this study did not need splitting ，and the yield of the technology was significantly higher than that of splitting technology reported in literature （31.9％）. The optimized technology reduced the generation of impurities and improved the product quality. CONCLUSIONS ：The improved technology has milder reaction conditions ，shorter synthesis route and higher yield.