Chemotherapy Anti-nausea Drug Group (Aprepitant) Synthesis And Process Of The Research

As the first neurokinin-1(NK-1) receptor blocker, aprepitant is mainly used for the treatment of chemotherapy-induced nausea and vomiting symptomatic. Since aprepitant approved by FDA in 2003, it has been going public in many countries and regions such as North America, Europe, Korea, Hong Kong and its like, with sales volume increased year by year.On the basis of analysis and comparison of different literatures at home and abroad, an appropriate route have been confirmed to synthesize aprepitant. In this paper, the synthesis process of this medicine were studied and optimized.,. With 4- benzyl- 2- hydroxy- 3-ketone morpholine as raw materials, through reactions including esterification reaction, etherification reaction and asymmetric transformation to synthesize the key intermediates of chiral pure(R)- 4- benzyl- 2- [(R) 1-(3, 5- two(three fluorinated methyl) phenyl] ethoxy] morpholine- 3 – ketone. Then by virtue of Grignard reaction and asymmetric catalytic hydrogenation reaction to synthesize aprepitant.Consequently, this synthesis routes possessed such advantages as simple isolation and purification processes, little byproducts, using earth-abundant catalysts and relativity high yield. Hence solved the limitation to scale-up productions caused by using expensiveoriginal reagents.Meanwhile, as part of our further research to aprepitant,we studied the synthesis method of its chiral moleculeand the characteristics of aprepitant’s different Crystal form.Finally, a verity of crystal forms were obtain by using various methods.