抗精神病药利培酮的合成

Synthesis of Antipsychotic Drug Risperidone

设计并验证1条利培酮合成路线,4-哌啶甲酸通过乙酰化、氯化、傅克、水解、肟化、环合共6步合成6-氟-3-(4-哌啶基)-1,2-苯并异噁唑,2-氨基吡啶经环氯化、加氢还原2步合成2-甲基-3-(2-氯乙基)-6,7,8,9-四氢吡啶并(1,2-α)嘧啶-4-酮,所得2个化合物经缩合反应得到利培酮,总收率12%。氯化反应选择二氯乙烷作为溶剂有利于分离,以钯炭为最佳催化剂,最佳用量为质量分数5%。该合成路线具有工艺条件温和、原材料易得等优点,适合工业化生产。

A process for risperidone synthesis was designed and validated. 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride was synthesized from 4-piperidinecarboxlic acid through acetylation, chlorination, Fiedel crafts reaction, hydrolysis, oximation and cyclization. 3-(2-Chloroethyl)-6,7,8,9-tetrahydro-2-methyl- 4H-pyrido[1,2-α]pyrimidin-4-one was synthesized from 2-aminopyridine in 2 steps of condensation and hydrogenation reduction. Risperidoneis obtained from the two compounds through condensation, in the total yield of 12%. 1,2-Dichloroethane is used as a solvent for the separation with palladium on carbon as the best catalyst, the best dosage is 5% by mass. The process conditions are mild and raw materials are easily available, which is suitable for industrialization production.