CAJ | 학술논문

目的：优化抗精神病药伊潘立酮1的合成工艺以适用于工业化生产。方法以4-哌啶甲酸、乙酸、乙酸酐为起始原料，经酰胺化、酰氯化、傅－克酰基化反应、水解得到2，4-二氟苯基-4-哌啶基甲酮盐酸盐4，再经肟化、分子内环合、成盐得6-氟-3-（4-哌啶基）-1，2-苯并异唑盐酸盐2。2和4-（3-氯丙氧基）-3-甲氧基苯乙酮在碱催化下缩合得到伊潘立酮1。结果与结论对反应物配比、催化剂用量、反应温度及时间等因素进行了优化研究，使得该合成方法反应条件温和、易控制，副反应少，后处理简单，总收率可达34．9％（以4-哌啶甲酸计），其结构经IR、1 H-NMR和MS确证。
목적：우화항정신병약이반립동1적합성공예이괄용우공업화생산。방법이4-고정갑산、을산、을산항위기시원료，경선알화、선록화、부－극선기화반응、수해득도2，4-이불분기-4-고정기갑동염산염4，재경우화、분자내배합、성염득6-불-3-（4-고정기）-1，2-분병이서염산염2。2화4-（3-록병양기）-3-갑양기분을동재감최화하축합득도이반립동1。결과여결론대반응물배비、최화제용량、반응온도급시간등인소진행료우화연구，사득해합성방법반응조건온화、역공제，부반응소，후처리간단，총수솔가체34．9％（이4-고정갑산계），기결구경IR、1 H-NMR화MS학증。
Objective To optimize the synthesis process of iloperidone 1 for industrial production.Methods Piperi-dine-4-carboxylic acid, acetic acid and acetic anhydride were used as starting materials to generate 2 via amidation, Friedel-Crafts acylation, hydration, oximation, intramolecular cyclization and salification.Compound 2 was treated with 4-(3-chloropropoxy)-3-methoxyphenylethanone through condensation to afford iloperidone.The target compound 1 was prepared with an overall yield of 34.9%.Results and Conclusion Such factors as the ratio of the raw materials, the catalyst, reactive time were investigated and optimized to make the reaction conditions mild and easy to control with less side effects.The structure has been confirmed by IR, 1 H-NMR and MS.