Improved Industrial Synthesis of Antidepressant Sertraline

Abstract

(cis-1S)-4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine hydrochloride, or sertraline hydrochloride, is a very effective antidepressant. This report presents a novel industrial synthesis of sertraline hydrochloride that is in many respects more advantageous than processes reported thus far. N-[4-(3,4-Dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]-methanamine N-oxide is used as intermediate in our process, which is a stable compound in normal conditions. It can be obtained in a simple reaction from the corresponding tetralone in good yield, using acceptable reagents with regard to environmental and safety respects. Its reduction to the desired cis-racemic amine is stereoselective, and thus it provides sertraline hydrochloride with a purity required for pharmaceutical ingredients.