858126-22-4Relevant academic research and scientific papers
Production method of Ezetimibe intermediate
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Paragraph 0032; 0033; 0034; 0040; 0041; 0042, (2017/08/29)
The invention discloses a two-stage three-step method for preparing an Ezetimibe intermediate. The method comprises the following steps: stage one, using common commodities such as p-hydroxy benzaldehyde and p-fluoro aniline as reactants and using water as a reagent, and carrying out heating condensation to generate Schiff base, wherein the yield can reach 97.0%; and stage two, the stage comprising two steps, firstly using a chiral reducing reagent R-CBS and borane dimethyl sulfide to reduce a starting material 1 and obtain an in situ intermediate; enabling the in situ intermediate to directly react with the Schiff base obtained in the stage one, so as to obtain the final product Ezetimibe intermediate, wherein the yield can reach more than 75.0%. In the first step of the second stage, a sulfuric acid solution, a 5% sodium sulfite solution and a 10% sodium chloride solution are used in sequence for washing an organic phase, and finally the organic phase is washed with water and is dried by using sodium sulfate, so that various organic and inorganic impurities are sufficiently removed, and the in situ intermediate is not separated, but the purity is high. The prepared in situ intermediate reacts with the Schiff base, so that the Ezetimibe intermediate is high in yield and high in purity.
