湖北科技学院学报（医学版）2025，Vol.39Issue(5)：401-405,5.DOI:10.16751/j.cnki.2095-4646.2025031902
(S)-2-氰基-4,4-二氟吡咯烷对甲苯磺酸盐的合成
Synthesis of(S)-2-Cyano-4,4-Difluoro-Pyrrolidine p-Toluenesulfonate
摘要
Abstract
Objective To synthesize the DPP-4 inhibitor intermediate(S)-4,4-difluoropyrrolidine-2-carbonitrile p-toluenesulfonate.Methods The target compound was synthesized starting from N-Boc-trans-4-Hydroxy-l-proline methyl ester.The synthesis involved six steps:oxidation,fluorination,hydrolysis,amidation,dehydration,and deprotection to form a salt.Additionally,the effects of reaction conditions on the outcomes were investigated.Results The intermediate was obtained using TEMPO as an oxidation catalyst and DAST as a fluorinating a-gent,followed by lithium hydroxide hydrolysis,ammonium bicarbonate amidation,trifluoroacetic anhydride dehydration,and p-toluenesulfonic acid de-Boc protection,with an overall yield of over 60％.Conclusion This synthetic route is easy to operate,with simple post-processing and high yields,and provides a reference for synthetic research related to DPP-4 inhibitors.关键词
(S)-2-氰基-4,4-二氟吡咯烷对甲苯磺酸盐/合成/DPP-4抑制剂Key words
(S)-4,4-difluoropyrrolidine-2-carbonitrile p-toluenesulfonate/Synthesis/DPP-4 inhibitor分类
医药卫生引用本文复制引用
刘春燕,李倩,梁梓健,吴诗,郭丽媛,黄胜堂..(S)-2-氰基-4,4-二氟吡咯烷对甲苯磺酸盐的合成[J].湖北科技学院学报（医学版）,2025,39(5):401-405,5.基金项目
湖北科技学院校内培育科研项目(2018-19X040) （2018-19X040）
湖北科技学院药学院2018年度药学重点学科专项科研项目(2019-20ZY16) （2019-20ZY16）
