Synthesis Of Duloxetine Hydrochloride

Duloxetine hydrochloride (Duloxetine hydrochloride) chemical name (S)-N-methyl-3-(1-naphthyloxy)-2-thienyl hydrochloride, is a 5-hydroxytryptamine (5-HT) and norepinephrine (NE) reuptake inhibitors a double.In this thesis, the literature on duloxetine reported improved synthetic route, using a new process route to 2-acetyl thiophene raw materials and dimethylamine hydrochloride and paraformaldehyde Mannich reaction occurs, and then by sodium borohydride reduction, and 1-fluoride alkylation of naphthalene occurred, the chloroformate N-methyl-off, and finally by the S-(+)-mandelic acid split in the system. Specific synthetic route is as follows:1) N, N-dimethyl-1-(2- thienyl)-1-acetone Hydrochloride Synthesis: 2- acetyl thiophene as starting material, the classic Mannich reaction, synthesis yield was 89.5%.2) N, N-dimethyl-3-hydroxy-1-(2- thienyl)-1-propylamine synthesis: use of sodium borohydride reduction reaction yields were 88.6%.3) N, N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)-1-propylamine Synthesis: with 1- fluoro naphthalene was synthesized yield of 90.5%.4) N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)-1-propylamine: the demethylation reaction, yields were 92.8%.5) the synthesis of duloxetine: The last use of S-(+)- mandelic acid into racemic hydrochloride, synthetic yield of 47.8%.Thesis and synthesis of the intermediate structure of the final product by IR spectroscopy (IR), mass spectrometry(MS), nuclear magnetic resonance spectroscopy (HNMR) and carbon nuclear magnetic resonance spectroscopy (13CNMR) spectra.The route through the optimization of reaction conditions, integrated yield of 28.7%, more than has been reported in the literature of other synthetic routes yield obtained.In this thesis, the synthetic route chosen, the innovative product will restore the last step to split into, thus avoiding the DL, and to improve product purity and quality. Reaction in the ether phase transfer catalyst is added, is an innovative point.