| 引用本文: | 何光超,王均伟,管哲,朱启华,徐云根.盐酸绿卡色林的工艺研究[J].中国现代应用药学,2019,36(9):1067-1070. |
| HE Guangchao,WANG Junwei,GUAN Zhe,ZHU Qihua,XU Yungen.Practical Synthesis of Lorcaserin Hydrochloride[J].Chin J Mod Appl Pharm(中国现代应用药学),2019,36(9):1067-1070. |
|
| 摘要: |
| 目的 研究减肥药盐酸绿卡色林（1）的合成工艺。方法 以N-烯丙基-N-[2-（4-氯苯基）乙基]氨基甲酸叔丁酯（3）为原料，经一步反应同时实现分子内的傅-克烷基化反应和脱Boc保护基反应，再经L-（+）-酒石酸手性拆分和成盐制备得到1。结果 合成工艺总收率为24.7%，化学纯度为99.9%，光学纯度ee值>99.8%。各中间体和目标产物经1H NMR、13C NMR、ESI-MS表征。结论 所研制的合成工艺路线操作简便、经济实用，适合工业化生产。 |
| 关键词: 盐酸绿卡色林 合成工艺 减肥药 |
| DOI：10.13748/j.cnki.issn1007-7693.2019.09.007 |
| 分类号:R914 |
| 基金项目:江苏省产学研前瞻性联合研究项目（BY2015072-02） |
|
| Practical Synthesis of Lorcaserin Hydrochloride |
|
HE Guangchao, WANG Junwei, GUAN Zhe, ZHU Qihua, XU Yungen
|
|
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China
|
| Abstract: |
| OBJECTIVE To study the synthetic process of antiobesity drug lorcaserin hydrochloride(1). METHODS 1 was synthesized form N-allyl-N-[2-(4-chlorobenyl)ethyl]tert-butyl carbamate(3) in a three-step process via one-step intramolecular Friedel-crafts alkylation and deprotection, chiral resolution with L-(+)-tartaric acid, and the final salification. RESULTS In overall yield was 24.7% the purity was 99.9%, and excellent enantioselectivity(ee) >99.8%. The intermediates and target product were confirmed by 1H NMR, 13C NMR and ESI-MS. CONCLUSION This convenient and economical procedure is remarkably applicable for industry. |
| Key words: lorcaserin hydrochloride synthesis process antiobesity drug |
