Synthesis And Production Technology Research Of Lorcaserin

In recent years, obesity-related diseases have seriously threatened human health, so the research of diet pills has received increasing attention. Lorcaserin is a kind of diet pills which acts on central nervous system, by stimulating the neurotransmitter serotonin of the central nervous system that it can suppress appetite. Different from other diet pills, Lorcaserin is a selective serotonin5-HT2C receptor agonists, which won’t cause heart valve disease and pulmonary hypertension, so it has a very high security and is widely concerned. In this dissertation, the synthetic route and production technology of Lorcaserin are studied. The main contents are as follows:(1) The synthetic routes of Lorcaserin were discussed. Finally, it was chosen that the route starts with2-(4-chlorophenyl)ethanol as the raw material, through bromination, amination, chlorination, Friedel-Crafts reaction and chiral resolution to get the target.(2) The synthetic process of the intermediate1-(2-bromoethyl)-4-chlorobenzene (B) was explored, the preferable reaction conditions are as follows:the molar ratio of2-(4-chlorophenyl)ethanol and phosphorus tribromide is2.5:1, reaction temperature is75℃, reaction time is2hours.(3) The synthetic process of the intermediate1-[[2-(4-chlorophenyl)ethyl]amino]-2-hydroxypropane(C) was explored, the preferable reaction conditions are as follows: the molar ratio of isopropanolamine and intermediate B is3:1, reaction temperature is90℃, reaction time is4hours.(4) The synthetic process of the intermediate1-[[2-(4-chlorophenyl)ethyl]amino]-2-chloropropane hydrochloride(D) was explored, the preferable reaction conditions are as follows:the molar ratio of thionyl chloride and intermediate C is2:1, reaction temperature is55℃, reaction time is3hours.(5) The synthetic process of the intermediate8-chloro-2,3,4,5-tetrahydro-1-methyl-lH-3-benzazepine(E) was explored, solid-state organic synthesis was used in this step, the preferable reaction conditions are as follows:the molar ratio of aluminium choride and intermediate D is1.5:1, reaction temperature is120℃, reaction time is3hours.(6) Acetone and water were chosen as solvent system, L(+)-tartaric acid was used to separate intermediate E to get (R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine tartrate(F). Then, potassium carbonate was used to dissociate intermediate F to obtain Lorcaserin.(7) The chemical structures of intermediates and Lorcaserin were characterized.(8) In the basis of optimized conditions of Lorcaserin, chemical process flow charts and production equipment flow charts of each intermediates and finaLproduct were established by studying enlarged production.