Levocabastine hydrochloride, R-50547, Livostin, Livocab, Levophta, Levocon, Livostin Nasal Spray

左旋多巴 左卡巴司丁 Chemical Name: (-)-[1(cis),3alpha,4beta]-1-[4-Cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenyl-4-piperidinecarboxylic acid monohydrochloride; (-)-trans-1-[cis-4-Cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenylisonipecotic acid monohydrochloride
CAS No. 79547-78-7, 79516-68-0 (free base)
项目整合开发状态: Launched-1991
项目研究机构: Janssen (Originator), Janssen-Cilag (Originator), Janssen-Kyowa (Originator), Chauvin (Licensee), Novartis Ophthalmics (Licensee), Santen (Licensee), Nippon Shinyaku (Comarketer)
合成路线:The title compound has been obtained by condensation of 4-amino-5-chloro-2-methoxybenzoic acid (I) with cis-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidine-4-amine (II) by means of DCC in dichloromethane or PCl3 in benzene.

合成路线:The reductive amination of 4-cyano-4-(4-fluorophenyl)cyclohexanone (I) with (-)-benzyl 3-methyl-4-phenyl-4-piperidinecarboxylate (II) by means of H2 and Pt/C 5% in the presence of thiophene in isopropyl alcohol at normal pressure and at 50 C gives a 9:1 mixture of (-)-benzyl [3S-[1(cis)-3alpha,4beta]]-1-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenyl-4-piperidinecarboxylate and (-)-benzyl [3S-[1(trans)-3alpha,4beta]]-1-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenyl-4-piperidine-carboxylate.Chromatographic separation [dry column,silica gel,eluted with organic phase of a mixture of chloroform and methanol (99.0:1.0 by volume) yields the pure (-)-benzyl [3S-[1(cis)-3alpha,methyl-4-phenyl-4-piperidinecarboxylate (III),which is hydrogenolized in tetrahydrofuran at normal pressure and room temperature.The resulting free carboxylic acid is transformed to the monohydrochloric acid in methanol.