Study On Synthesis Of Efavirenz And Quinoline Derivatives

Efavirenz is a orally effective non-nucleoside reverse transcriptase inhibitor usedfor treating human immunodeficiency virus type-I (HIV-1). Firstly, efavirenz wassynthesized via the5steps concluding desalination, amino protection, asymmetricaddition, deprotection reactions of amino, and cyclization from2-(trifluoroacetyl)-4-chloroaniline hydrochloride as materials(overall yield56%,purity>99.5%, ee%>99.9%). A practical and enantioselective synthesis route ofefavirenz, which is suitable for the manufacture, is now available. Efavirenz and itsintermediates were confirmed by NMR, MS, IR, HPLC, melting point analysis and soon.Secondly, after comparing the reported synthetic routes of impurity2a(2-cyclopropyl-4-trifluoromethyl-6-chloroquinoline), we designed a simple and greensynthetic route to prepare impurity2a (yield90%, purity>99.5%) and synthesize aseries of quinoline derivatives.Finally, to our surprise, we obtained a novel compound3a in the synthetic processof impurity2a and comfirmed its structure with a moiety of3-halogenated-4-trifluoromethyl quinoline after characterization. Through the optimization of the modelreaction, we established a simple route with a typical property of "one-pot" method andprepared a series of novel3-halogenated-4-trifluoromethyl quinoline derivatives. Themethod enrichs the synthetic means of quinoline heterocyclic compounds.