Synthesis Process Research Of Antidepressant Drug Sertraline Hydrochloride

Sertraline hydrochloride is a selective 5-serotonin re-uptake inhibitors, Pfizer Inc developed and put it into market in the 20th century, early 90s. It can help improve the body's ability to alleviate the patient's depressive symptoms, including irritability mood, and can reduce the symptoms of persistent fatigue and anxiety state. Sertraline hydrochloride, as a new type of antidepressant drugs are clinically favored by more and more people.In this paper, o-dichlorobenzene and 1-naphthol as raw materials and anhydrous aluminum chloride as catalyst, geting Sertraline key intermediate 4-(3,4-dichloro-phenyl)-1-tetralone by Friedel-Crafts reaction, and then condense with methylamine alcohol solution to get Sertraline imine. The Cis-Sertraline was got by reduction reaction, and D-(-)-mandelic acid as chiral resolving agent to optical rotation split, and react with HCl to get a pharmaceutical active Cis-(+)-Sertraline hydrochloride.In the synthesis process of intermediate 4-(3,4-dichloro-phenyl)-1-tetralone, this paper used the reactants o-dichlorobenzene as solvent, by single-factor experimental method and orthogonal test to determine the best experimental conditions. In the synthesis process of Sertraline imine, this paper refered to other information and based on reaction principle, added formic acid as catalyst to accelerate the reaction. In the process of Sertraline amine reduction, the paper chose several different methods, compared with sodium borohydride, sodium malonyloxyborohydride and palladium carbon hydrogenation. The results showed that palladium carbon hydrogenation catalysts was the best, Sertraline imine could be completely reduced under normal pressure.In the process of reaction, TLC monitored the reaction end, and use IR, NMR and the melting point method to determine the product structure.The total yield of this process was more than 20%, [α]20D=+38.3(C = 2.0 methanol), Chiral column: 99%. The synthesis process did not cause serious pollution, has lower cost, and there was the possibility to enlarge the production.