Synthetic Process Research Of Nebovolol Hydrochloride

In this thesis, p-fluoroanisole was used as raw material in the synthetic route, RSSS- nebivolol and SRRR- nebivolol were obtained via Friedel-Crafts reaction, Wittig reaction, Michael reaction, ketal hydrolysis, carbonyl reduction, TS esterification, epoxidation, ring opening benzylamine and hydrogenolysis of benzyl. The purity satisfied the India pharmacopoeia standard.The D,L-2,2-Dimethyl-1,3-dioxolane-4-carboxaldehyde was used as raw material and reacted with intermediate II via Michael addition which generated a chiral center. The p-fluorobenzoyl chloride was used in the next step. Through the controlling of feeding ratio and reaction conditions, the low selectivity and yield of intermediate VI in literature process were improverd. The high purity Nebivolol could be easily obtained by molten hydride. The similar synthetic processes from intermediate IV to intermediate IX simplified the procedures.In addition, the yield was improved from 1% to 3.9% and the cost of production was reduced by our new synthetic route. This synthetic process is valuable for industrial production. And the product was characterized by melting point, Element analysis, IR, X- ray powder diffraction and thermal analysis.