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 paminophenol to retinoic acid, and the total yield is 80. 7%.
