一种大规模合成N-(4-羟苯基)维甲酰胺的新方法

介绍了抗肿瘤药物N-（4-羟苯基）维甲酰胺（4-HPR）的合成新方法．该方法包括如下反应步骤：全反式维甲酸与二氯亚砜反应生成酰氯，再与三乙胺成盐，然后将得到的酰基铵盐与对氨基苯酚发生酰胺化反应，制得4-HPR．该方法解决了文献报道方法在大规模合成时存在的多种问题如后处理繁琐、收率低等，具有操作简单、反应条件温和以及产率高等特点．此外，研究了反应试剂的摩尔比对反应收率的影响，最佳摩尔比为二氯亚砜和对氨基苯酚物质的量分别是维甲酸物质的量的2倍和3倍，总收率为80．7％．

Novel process for large scale synthesis of N-(4-hydroxyphenyl) retinamide

A method to synthesize anticancer drug N-(4-hydroxyphenyl)retinamide(4-HPR)on a large scale is described.It consists of the preferred steps of reacting all-trans retinoic acid with thionyl chloride to form retinoyl chloride and then reacting with triethylamine to generate retinoyl ammonium salt which in turn is reacted with p-aminophenol to eventually produce 4-HPR.This process can overcome many scale-up challenges that exist in the methods reported in the literature and provide an easy,mild and high yield route for large scale synthesis of 4-HPR.Moreover,the effects of the molar ratios of the reagents on the yield are examined.The best molar ratios are a 2.0 molar equivalence of thionyl chloride and a 3.0 molar equivalence of p-aminophenol to retinoic acid,and the total yield is 80.7%.