Synthesis Of Antihistamine Fexofenadine

The application of antihistamine provides physician with valuable tools for the treatment of allergic disease. Compared with traditional antihistamines, such as terfenadine, fexofenadine has many merits, for example, it could not cause heart toxicity, while its effect of anti-hypersusceptibility is stronger, and security is higher. It has been accepted by most people. However, synthesis of low yield, high production cost factors severely restricts the promotion of fexofenadine. Therefore, to increase the efficient synthesis of fexofenadine is the key that to improve fexofenadine's clinical application.Currently, the synthesis of fexofenadine has been reported in the form of patents mainly. We have studied these patents and proposed a new synthetic route innovatively.α,α-dimethylbenzeneacetic acid,α,α-diphenyl-4-piperidine methanol as the started material, fexofenadine was synthesized via esterification, acylation, reduction, N-alkylation, hydrolysis. Firstly,α,α-dimethylbenzeneacetic acid yisuan was esterified with ethanol, PW/SiO2 as the catalyst. Compared with traditional acid catalyst, PW/SiO2 has its own advantages. When the reaction completed, the next proposal is easy and without pollution nearly. Then esterifiable product was acylated with 4-Chlorobutyryl chloride. Different results were obtained through changing reagent, mole of material, time, temperature, and so on. Acylated compound was reduced by NaBH4 in 95% ethanol. The reaction could be carried out in room temperature, not like methanol. The followed reaction was N-alkylation reaction and 4-[1-hydroxy-4-[4-(hydroxydiphenyl)-1-piperidine]-α,α-dimethylbenaene acetate was obtained. In the end, target product was obtained with a yield up to 48.0% after hydrolysis. Review the whole synthesis route, it will be accepted by enterprises and extended widely.