Stereospecific synthesis process for tretinoin compounds

摘要

A stereospecific synthesis process for tretinoin compounds comprises the following steps: using substituted triphenyl phosphine salt and β-formyl crotonic acid as raw material to carry out WITTIG reaction under the action of alkali; then adjusting the pH of the reaction liquid to 5-10; adding palladium compound or rhodium compound to carry out isomerization directly and obtain tretinoin compounds with desired configuration. The product yield of the process is high and the intermediate product in the reaction dose not need to be separated. The process is easy to operate and can save the production cost and as well is suitable for industrial production.

主权项

1. A process for preparing compound of the Formula I comprises: performing WITTIG reaction under the action of alkali with the substituted tri-phenyl phosphonate (Formula II) and β-formoxyl crotonic acid (Formula III) as raw materials; then performing isomerization by adding palladium compound or rhodium compound to obtain the product compound of Formula I with desired configuration, characterized in that:
1) there is no need to perform hydrolysis after the WITTIG reaction; 2) there is no need to separate the products of WITTIG reaction, but performing isomerization directly; the WITTIG reaction and the isomerization are conducted continuously in one container; 3) adjusting the pH of reaction liquid to 5-10 by adding acid before the isomerization; in Formula I, the carbon-carbon double bonds on site 2-3, site 4-5 and site 6-7 have cis or trans configuration; in Formula II and Formula III, the carbon-carbon double bonds on site 2-3 have cis or trans configuration; in Formula I and Formula II, A is substituted unsaturated hexatomic carbocyclic group; X is selected from Cl, Br or HSO4.