| Mivacurium Chloride was a short-acting nondepolarizing ester neuromuscular blocking drug in clinic. 3,4,5-trimethoxyphenylacetic acid was an important intermediate of Mivacurium Chloride. It was mainly import and the supply was finite and very expensive. So, the synthesis procedure has been optimized and improved in order to make it more convenient than that in literature.A new synthetic routes of 3,4,5-trimethoxyphenylacetic acid has been explored. Firstly, 3,4,5-trimethoxybenzaldehyde was synthesized through through bromination, methoxy-reaction, methylation by vanillin. Phase transfer catalysis was taken in turn to synthesize 3,4,5-trimethoxymandelic acid. Lastly 3,4,5-trimethoxyphenylacetic acid was prepared through dehydroxy-reduction by chlorotri-methylsilane. A satisfactory results has been got in the first and last steps, but the second step must be improved.This paper described in detail the various steps of the process conditions, discussed and compared the impact of product quality and yield of the main factors that drew the best reaction conditions:Bromination:reaction temperature 5-10℃,reaction time 6h, vanillin 15.2g, HBr(40%) 180mL, H2O2(30%) 23mL, alcohol 30mL, yield 96.2%.Methoxy-reaction:reaction temperature 90-95℃, reaction time 2.5h,5-bromovanillin 10g, sodium 4.9g, methanol 100mL, DMF 5mL, yield 84.6%.Methylation:reaction temperature 90℃, reaction time 12h, syringaldehyde 15.3g, K2CO3 13.8g, DMC9.0g, yield 93.2%.Phase transfer catalytic reaction:reaction temperature 60℃, reaction time 7h, NaOH(40%), catalysts: CTMBA and PEG-600, yield 70.3%.Reduction:reaction temperature 80℃, reaction time 5h,3,4,5-trimethoxymandelic acid 9.7g, chlorotri-methylsilane 5.4g, sodium iodide 7.5g, glacial acetic acid 2mL, zinc powder 1g, yield 91%.
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