1-(双(4-氯苯基)甲基)哌嗪的便捷合成

Simple Synthetic of 1-(4,4-Dichlorbenzhydryl)Piperazine

1-(双(4-氯苯基)甲基)哌嗪是合成ML-210的重要中间体,其以4,4’-二氯二苯甲酮为起始原料,经还原、氯代、取代3步反应得到.在合成过程中,探讨了还原反应的影响因素,并探讨了温度对取代反应收率的影响,得出最佳反应条件为:还原反应中还原剂硼氢化钠与4,4’-二氯二苯甲酮物质的量比为2:1,取代反应温度为85℃,产物合成的总收率为62.17%,纯度97.5%,并通过1H NMR、LCMS对产物进行结构确认.研究简化了合成路线,提高了收率,有利于工业化生产.

1-(4,4-Dichlorbenzhydryl)piperazine is an important intermediate for the synthesis of ML-210.It takes 4,4’-dichlorobenzophenone as the raw material,and obtains the product through three steps such as reduction,chlorination and substitution reaction.During the synthesis process,we discussed the influencing factors of the reduction reaction,and the influence of temperature on the yield of the substitution reaction.The best reaction condition in the reduction reaction is that the ratio of the reducing agent sodium borohydride to 4,4’-dichlorobenzophenone is 2:1.The optimal temperature for the substitution reaction is 85°C.The total yield of the product is62.17%,and the purity is 97.5%.Meanwhile,we confirmed the structure of the product by 1H NMR and LCMS.This optimized synthetic process improves the yield and is beneficial to industrial production.