A Syntheis Process For The Critical Intermediate Of VDAs Medicine Vadimezan

Vascular disrupting agent(VDAs)is a kind of critical medicine,which can rapidly selective destroy the new tumour vascular to cure the cancer.Vadimezan,2-[2-(Carboxylmethyl)phenoxy]-3,4-dimethylbenzoic acid(ASA404),is a type of VDA and usually used together with other drugs to cure the advanced lung cancer and other tumors.2-[2-(Carboxylmethyl)phenoxy]-3,4-dimethylbenzoic acid is a key intermediate in the synthesis of ASA404.However,this process has many disadvantages,such as low yield,high cost of raw materials,and many by-products.According to the literatures,firstly 2,3-dimethylaniline,trichloroacetaldehyde and hydroxylamine hydrochloride were used to prepare 2-amino-3,4-dimethyl benzoic acid.Then sodium 2-iodo-3,4-dimethyl benzoate was synthesized.Finally this intermediate reacted with 2-hydroxyphenylacetic acid to synthesize the target product 2-[2-(Carboxylmethyl)phenoxy]-3,4-dimethylbenzoic acid.In the paper,the amount of key raw materials including trichloroacetaldehyde,hydroxylamine hydrochloride,2-hydroxyphenylacetic acid and iodine,etc.were determined.The results showed that the total yield of the product was about 60% and higher quality products could be obtained.It was also found that cheaper raw materials were also effective in the reaction and reduced the cost.The process studied in the paper would be more suitable for industrial production and meet the requirements of quality control specifications.