The Asymmetric Synthesis Of Fexafenadine

Fexafenadine is a lastest drug for anti-hypersusceptibility drugs in recent years and has the a vast marketplace prospect. Fexafenadine has many merits, for example, it would not cause heart toxicity or lethargy, while its effect of anti-hypersusceptibility is stronger , and security is higher. At present, drugs produced domestically and abroad are Fexafenadine's raceme. Since racemic drugs have induced a series of problems in actual application, such as drug effect, metabolize, toxicity, the study on chirality drugs have already become one of world's new direction and hot spot which will provide pledge for validity and security in drugs' application, since racemic drugs have induced a series of problems in actual application. We believe that Fexafenadine will have higher value of practical application and stronger market competition.α,α-dimethylphenylethyl acetate, which is the key intermediates of fexafenadine, is usually achieved by three to four steps' reaction. We have synthesized the intermediates by only one step, taking benzene andα-ethyl methacrylate as raw material, Fexafenadine's synthesis route was facilitated and we decreased the reaction steps of original main body reaction from eight to five. However, the reaction yield was not high, mainly as the reaction is a Friedal-Crafts reaction in benzene ring, besides, the benzene ring's activation after alkyl, effects of many substituted reactions and the stability of carbon cationic, all these have influenced the result.Since (Ipc) ₂BH was introduced to asymmetric hydrogenation reaction first in 1961, theα-pinene and its derivative boron reagent have been testified to be the effective reagent to make use of organic boron to process asymmetric synthesis reagent. We have taken benzene andα-pinene as raw material, the chirality deoxidization reaction carrying out on selected compound take this as chirality ligands.In the thesis, we have chosen a series of the verification being in progress with Fexafenadine carring out conditional preparation by screening of reaction with the charagteristic of structure similarity in the carbonyl compound fixing, and validated the choosing efficiency of chirality ligands' asymmetrically. The simplest structure hypnone arrived at the simple Fexafenadine's intermediate and then arrived at the complicated structure compound having the similarly basic group with Fexafenadine, with excellent antipode selectivity. Finally, we had synthesized the extremely high optics purity S-configuration of Fexafenadine.Since the time of experiment is restricting, we were not able to compare more chirality ligands to the carbonyl compound's reaction efficiency and antipode selectivity, also failed to choose right chirality ligands to compose Fexafenadine's R- configuration.