The Optimization Synthesis Of Loxoprofen Sodium Intermediates

2-(4-bromomethylphenyl) propanoic acid is one of the key intermediates for synthesizing Loxoprofen sodium. Use toluene as start material, the 2-(4-bromomethylphenyl) propanoic acid has been obtained through Friedel-Crafts acylation, ketalization, rearrangement and bromination. In the process of rearrangement,2-(4-methylphenyl) propanoic acid was synthesised by rearrangement of ketalization using zinc acetate as the major catalyst and cuprous chloride as the promoter. The effects of amount of reaction time, reaction temperature and catalyst on yield of 2-(4-methylphenyl) propanoic acid were investigated. The experiment results showed that the maximum yield of 89% could be obtained when reaction for 4.5h using 8.1g ketal,0.7g and 0.5g zinc acetate and cuprous chloride respectively at temperature of 140℃. In the process of bromination, the effects of different solvents and brominized agents were researched. The effects of the dropping time of bromine, molar ratio of reactants, the contents of solvent and initiator of BPO on yield of 2-(4-bromomethylphenyl) propanoic acid were examined. The experiment results showed that the maximum yield was up to 50% when 2-(4-methylphenyl) propanoic acid was 9.84g, dropping time of bromine was 5h, molar ratio was 1, the contents of chloroform and BPO were 40mL and 0.7g respectively. Futhermore, the mechanism of rearrangement and bromination was explored.The X-4 micro melting point detector, HPLC, IR and 1HNMR were used to analysis and characterize the products.