盐酸司来吉兰的经典合成路线使用安非他明或(–) -(R) - 甲基苯丙胺作为起始原料，涉及管制品，对企业来说获得生产许可的难度很大。近年来报道的新合成方法多需经历叠氮化、格氏反应等危险操作，收率低、成本较高，不易实现工业化生产。本研究以N,N- 二甲基-(S)-2- 苄基- 氮杂环丙烷基-1- 磺酰胺( 可比司他中间体) 为手性源，经硼氢化钠开环、缩合、脱保护、胺化还原得到盐酸司来吉兰。本工艺反应条件温和，后处理只需采用重结晶、成盐等简便操作，无需柱色谱分离等，更适合工业化生产，总收率约29.4％。
Abstract
The classic synthetic route of selegiline hydrochloride uses amphetamine or(–)-(R)- methamphetamine, which are classified as controlled substances, as the starting material, so it is difficult for enterprises to obtain the production license. Most of the new synthetic methods reported in recent years involved some dangerous operations such as azide and Grignard reactions, with low yields and high cost. In this study, selegiline hydrochloride was synthesized from the chiral pool compound N,N-dimethyl-(S)-2-benzyl-aziridine-1-sulfonamide(the intermediate of cobicistat) via ring-opening reaction, condensation, deprotection and reductive amination. The reaction conditions of this process were mild, the post-processing only needed simple operations such as recrystallization and salification, and didn't need column chromatographic separation. This process with a total yield of 29.4％ was more suitable for industrial production.
关键词
司来吉兰 /
合成 /
开环反应 /
缩合 /
脱保护 /
胺化还原
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Key words
selegiline /
synthesis /
ring-opening reaction /
condensation /
deprotection /
reductive amination
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参考文献
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