A method for solid phase synthesis of a beraprost sodium intermediate

Abstract

This invention belongs to the field of organic synthesis technology, specifically relating to a solid-phase synthesis method for a beraprost sodium intermediate. The solid-phase synthesis method includes the following steps: 4-(3-bromo-2-hydroxyphenyl)butyric acid is attached to a resin, then sequentially undergoes a coupling reaction with cyclopentadiene monoepoxide, a cyclization reaction with allyltributyltin, a double bond shift reaction with tris(triphenylphosphine)carbonylruthenium hydrochloride, and sequential ozonolysis and reduction reactions with ozone and sodium borohydride. Finally, the product is cleaved from the resin and methylated to obtain the beraprost sodium intermediate. This invention attaches 4-(3-bromo-2-hydroxyphenyl)butyric acid to a resin, and the target product in each step can be separated from the solvent and excipients through simple solid-liquid separation and washing, eliminating the need for column chromatography purification. The operation is simple and conducive to large-scale production.

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