Synthesis of Methyl p-Bromomethylcinnamate as the Key Intermediate of Ozagrel Sodium
The intermediate of p-methyl cinnamate was produced by Claisenschmidt condensation reaction with the materials of p-methyl benzaldehyde and methyl acetate.The reaction conditions were optimized as follows:the mass ratio of methyl acetate to p-methylbenzaldehyde was 5∶1,the molar ratio of sodium methanol to p-methylbenzaldehyde was 2.0∶1.0,and the reaction temperature was 65 ℃.Under the optimized conditions,the yield and content of methyl p-methylcinnamate were 92.32％and 99.38％respectively.The key intermediate of ozagrel sodium was obtained by the reaction of methyl p-methyl-cinnamate with N-bromosuccinimide(NBS).The reaction conditions were optimized as follows:the solvent was methyl acetate,the mass ratio of methyl acetate to methyl p-methylcinnamate was 4∶1,the reaction temperature was 70 ℃,and the molar ratio of NBS to methyl p-methylcinnamate was 1.2∶1.0.Under optimized conditions the yield and purity of NBS were 88.86％and 97.48％,respectively.The process has the advantages of green environmental protection,high yield and low cost.
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