摘要
目的 优化枸橼酸舒芬太尼的绿色合成工艺.方法 以N-叔丁氧羰基-哌啶酮、苯胺及2-(2-噻吩)乙醇为原料,经Bargellini、酯化、还原、甲基化、脱保护、磺酰化、N-烷基化、酰化反应得舒芬太尼,最后经成盐得枸橼酸舒芬太尼.结果 优化后的绿色合成工艺避免了使用剧毒试剂氰化物及钯炭加氢脱苄基工艺,终产品的纯度可达99.5％以上.结论 优化后的枸橼酸舒芬太尼合成工艺,原料廉价易得,反应条件温和,操作简便,工艺安全性高,可保证药品的质量及安全性,适合绿色工业化生产.
Abstract
Objective To optimize the green synthesis process of sufentanil citrate.Methods With N-Boc-piperidone,aniline,and 2-(2-thiophene)ethanol as active pharmaceutical ingredients(API),sufentanil was obtained through Bargellini,esterification,reduction,methylation,deprotection,sulfonation,N-alkylation,and acylation reactions.Finally,sufentanil citrate was obtained by salt formation.Results The optimal green synthesis process avoided the use of highly toxic reagents cyanides and palladium on carbon hydrogenation debenzylation processes,and the purity of the final product could reach over 99.5％.Conclusion The optimal synthesis process of sufentanil citrate has the advantages of cheap and easily obtainable API,mild reaction conditions,simple operation,and high process safety,which can ensure the quality and safety of the drug and is suitable for green industrial-scale production.
基金项目
重庆英才计划"包干制"项目(cstc2021ycjhbgzxm0315)
维普
万方数据