OBJECTIVE:To optimize the synthesis technology of 4-biphenylacetic acid,and to provide technology support to meet the market demand of 4-biphenylacetic acid raw material. METHODS:The synthesis route of 4-biphenylacetic acid from biphenyl by Friedel-Crafts reaction,ketal reaction,rearrangement reaction and hydrolysis was optimized and improved. The effects of different Friedel-Crafts reaction solvents (petroleum ether,dichloromethane,1,2-dichloroethane),ketal reaction ethanol (ethanediol, 1,3-propanediol, dimethyltrimethylene glycol, pentaerythritol), rearrangement reaction catalyzer (zinc biphenyl acetate,zinc oxide,zinc caprylate,zinc acetate) and refined solvent (isopropanol,95% isopropanol,ethanol,acetone,ethyl acetate) on synthesis technology were investigated. The optimal synthesis technology was screened with the purity and yield of intermediate or 4-biphenylacetic acid. RESULTS:The petroleum ether as Friedel-Crafts reaction solvent,ethylene glycol as ketal reaction ethanol,zinc diphenylacetate as rearrangement catalyst and 95% isopropanol as refining solvent were used for the preparation to obtain better effects. The yield of key intermediate 2′-chloroacetophenone reached above 95%. The purity of refined 4-biphenylacetic acid reached 99.9%;the content of single impurity was less than 0.1%;the total yield reached over 70%. CONCLUSIONS:The optimal synthesis technology of 4-biphenylacetic acid has the advantages of simple operation,mild and controllable reaction conditions,low cost,greener reagents and higher safety,and is suitable for industrial production. The purity and yield of the products are in high level and in line with the standards of European Pharmacopoeia and the Japanese Pharmacopoeia.