Synthesis of 3,4,5-Trimethoxyphenyl Acetic Acid

3,4,5-Trimethoxyphenyl acetic acid,an important intermediate for preparation of mivacurium chloride,was synthesized from 3,4,5-trimethoxybenzaldehyde by dichlorocarbene reaction and reduction reaction.The optimum reaction conditions are as follows:(1)In dichlorocarbene reaction,the molar ratio of raw materials was n(3,4,5-trimethoxybenzaldehyde)∶n(chloroform)=1∶3(based on 0.3 mol 3,4,5-trimethoxybenzaldehyde),w(NaOH)=40% solution was 21 mL,the composite phase transfer catalyst(PTC) was 2 g,reaction time was 7 hours at 60 ℃.The yield of 3,4,5-trimethoxymandelic acid was 71.7%.(2)In reduction reaction,the molar ratio of raw materials was n(3,4,5-trimethoxymandelic acid)∶n(trimethylchlorosilane)∶n(sodium iodide)∶n(zinc)=1∶1.25∶1.25∶3(based on 0.1 mol 3,4,5-trimethoxymandelic acid),one-pot reaction time was 5 h at 80 ℃.The yield of the target product was 91.0%.The overall yield of the two steps of reaction reached 65.2% and the structures of the target compound were confirmed by means of IR and 1HNMR.