189028-93-1Relevant articles and documents
Ezetimibe intermediate and preparation method of ezetimibe
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Paragraph 0098-0099, (2020/08/27)
The invention relates to an ezetimibe intermediate and a preparation method of ezetimibe. The ezetimibe intermediate has a structure as represented by a formula (I). The preparation method comprises the following steps: providing a compound represented by a formula (II); subjecting the compound as shown in a formula (II) to an asymmetric catalytic hydrogenation reaction under the action of a P-BIAMH catalyst to prepare a compound shown as the formula (I), wherein the P-BIAMH catalyst has a structure as shown in a formula (A) which is described in the specification. In the formula (A), X and Yare halogen independently; R1 is H or a C1-9 alkyl group; R2 is a high-molecular polymer; and a fragment as described in the specification represents a diphosphorus ligand. The method has the advantages of high conversion rate and high safety, and is especially suitable for industrial production.
according to folds Mai Bu and its intermediate synthesis method
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Paragraph 0063; 0064; 0065; 0066, (2017/07/26)
The invention provides an Ezetimibe synthesis method comprising the following steps: (a) a compound (5) is subjected to asymmetric reduction reaction to obtain a compound (6), and the compound (6) and tert-butyldimethylsilyl chloride react in an organic solution under the action of alkali to obtain a compound (7); (b) the compound (7) and diisopropylethylamine are dissolved in the organic solution, titanium tetrachloride is added in the organic solution to react at 20-50 DEG C, and a compound (3) is added in the organic solution at minus 20 to minus 60 DEG C to react to obtain a compound (8); (c) the compound (8) and N,O-bis(trimethylsilyl) acetamide react in the organic solution at 20-80 DEG C, tetrabutylammonium fluoride trihydrate is added into the organic solution to react at 20-80 DEG C to obtain a compound (9); (d) the compound (9) is subjected to off-protection reaction to obtain Ezetimibe, wherein R is equal to TBS, Ac or COOCH2CCl3. The invention further provides an Ezetimibe intermediate and a preparation method thereof.
Efficient and scalable process for the synthesis of antihypercholesterolemic drug ezetimibe
Zhu, Yijun,Pan, Jing,Zhang, Shunli,Liu, Zhenren,Ye, Deyong,Zhou, Weicheng
supporting information, p. 1687 - 1693 (2016/10/21)
An efficient and scalable process for the synthesis of antihypercholesterolemic drug ezetimibe through chiral Evans auxiliary (S)-4-phenyl-2-oxazolidinone is described. The key steps in this process are the condensation of (S)-3-(5-(4-fluorophenyl)-5,5-dimethoxypentanoyl)-4-phenyloxazolidin-2-one and N-(4-((tert-butyldimethylsilyl)oxy)benzylidene)-4-fluoroaniline, and the stereoselective reduction of ezetimibe-ketone with NaBH4/I2, which is first applied in the synthesis of ezetimibe. The process is concise, mild, easy to operate, and highly stereoselective (99.6% of de value of ezetimibe). In addition, three diastereomers of ezetimibe are synthesized and served as the references in quality control of the product.