Progress in Synthesis of S-metoprolol and Its Key Intermediates
The review describes the chemical total synthesis process of S-metoprolol.The synthesis of S-metoprolol begins with the separation of racemic epichlorohydrin,followed by reaction with the key intermediate 4-(2-methoxyethyl)phenol.4-(2-Methoxyethyl)phenol can be synthesized from phenylethanol,p-chlorophenol,phenol,p-hydroxyacetophenone,p-hydroxyphenylacetate methyl ester,p-nitrotoluene,and other raw materials.The synthesis of this intermediate from phenylethanol has the most industrial cases and the lowest cost,but it carries a high risk during the nitrification reaction.Due to the production of by-product metal salts and the challenges of waste treatment,there are fewer enterprises using the p-chlorophenol and phenol processes.The processes of hydroxyacetophenone and methyl p-hydroxyphenylacetate are still in the research stage and have certain development prospects.
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