Study On The Synthesis Of Dextropine Hydrochloride

Dexmedetomidine hydrochloride (trade name:Precedex, Dexdor) is a sedative medication used by intensive care units and anesthetists. In the present dissertation, its synthetic routes reported in the literatures were summarized, and a new synthetic protocol was designed. Thus, imidazole, a cheap and readily available stock, was treated sequentially with with N,N-dimethylformamide chloride and tert-butyl dimethyl chlorosilane to give the N(1)-and C(2)-protected imidazole2. Acylation of imidazole2with2,3-dimethylbenzoyl chloride afforded4-benzoylimidazole4a. From4a, the key intermediate of racemic dexmedetomidine7was prepared by Grignard addition, acidic dehydration and hydrogenation.Finally, the racemic7was resolved by treatment with L-(+)-tartaric acid to furnish8b. The target compound,(+)-4-(S)-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole monohydrochloride8a, was successfully obtained by basic treatment and salification with hydrochloride in ethanol.The condition for each of the synthetic steps of dexmedetomidine hydrochloride was optimized. Process investigation was also performed to adapt industrial production.