Study On The Synthesis Of Antihistamines Levocabastine Hydrochloride

Levocabastine hydrochloride,a long-acting second antihistaminic agent,which exhibits low central nervous system activity indicative of non-sedation,is mainly used to relieve or eliminate the allergy-induced allergic rhinitis.Nowadays Levocabastine hydrochloride has dominated the market among the second antihistamine because of its little side effect,high safety and convenience.It’s welcome by the majority of doctors and patients,and currently available in many countries worldwide.Nowadays,no method of synthesis of levocabastine hydrochloride has been described in detail in literature.In this paper,a route for the synthesis of levocabastine hydrochloride was designed and levocabastine hydrochloride was synthesized successfully.First,2-aminoethanol and(S)-(-)-Propylene oxide were used as the starting raw materials to synthesize the side chain one(3-methyl-4-phenyl-piperidine-4-carboxylic acid ethyl ester)through amination,Ts-protecting,chlorination,cyclization,hydrolysis,split,esterification and de-Ts.The intermediates were characterized by NMR and FT-IR.Then,4-fluorophenylacetonitrile and methyl acrylate were used as the starting raw materials to synthesize the side chain two(1-(4-fluoro-phenyl)-4-oxo-cyclohexanecarbonitrile)through Michael addition,cyclization and hydrolysis.Finally,levocabastine hydrochloride was synthesized by couloping of side chain A and side chain B.The levocabastine hydrochloride and intermediates were characterized by NMR and FT-IR.