河北科技大学学报2018，Vol.39Issue(2)：154-158,5.DOI:10.7535/hbkd.2018yx02009
(2S,4S)-N-叔丁氧羰基-4-氟脯氨酸的合成
Synthesis of (2S,4S)-N-tert-butoxycarbonyl-4-fluoroproline
摘要
Abstract
In order to overcome the difficulty to separate and purify the intermediate,solve the problem of quaternary ammoni-um salt removal,the synthesis of (2S,4S)-N-tert-butoxycarbonyl-4-fluoroproline which is a key intermediate of polypeptides and peptidomimetic drug is studied.The target compound is synthesized from (2S,4R)-4-hydroxyproline via esterification, amino protection,and hydroxyl activation-fluorination-hydrolysis tandem reaction.Hydroxyl activation,SN2 fluorine substitu-tion and ester hydrolysis reaction are completed as a tandem reaction.After the hydrolysis reaction,the product is precipitated from the aqueous solution during the process of adjusting the pH,and the target compound can be directly obtained through fil-tration.The reaction factors and parameters are optimized,The optimized conditions are as follows:in esterification reaction, n(SOCl2):n(substrate)=1.2:1.0;in amino protection reaction,n((Boc)2O):n(compound 1)=1.2:1.0;in trifluorom-ethyl sulfonylation reaction,n((Tf)2O):n(compound 2)=1.1:1.0,n(pyridine):n(compound 2)=1.2: 1.0.The total yield rate is 57.9% after optimization,and the purity is 98.3%.The structure of target compound is confirmed by 1H-NMR and 13 C-NMR.This protocol has advantages of mild reaction conditions and simple operation,and is suitable for industrial produc-tion.关键词
有机合成化学/非天然氨基酸/中间体/串联反应/SN2反应Key words
organic synthesis chemistry/unnatural amino acids/intermediates/tandem reaction/SN2 reaction分类
化学化工引用本文复制引用
刘甜甜,张志光,杨媛媛,马彦涛,张勇..(2S,4S)-N-叔丁氧羰基-4-氟脯氨酸的合成[J].河北科技大学学报,2018,39(2):154-158,5.基金项目
河北省引进留学人员资助项目(C2013003018) （C2013003018）
