(2S,3S)-3-N-叔丁氧羰基-1,2-环氧基-4-苯基丁烷的合成工艺优化

An Optimized Preparing Process for Tert-butyl(S)-1-((R)-oxiran-2-yl)-2-Phenylethylcarbamate

(2S,3S)-3-N-叔丁氧羰基-1,2-环氧基-4-苯基丁烷是多种HIV蛋白抑制剂的重要合成切块。本研究针对这个重要中间体的合成工艺进行了优化。整个工艺最关键的步骤为用N,N'-羰基二咪唑为活化试剂,一锅两步法直接合成亚砜叶立德中间体(3),避免了活性酰胺中间体(2)的纯化。本研究对还原反应也进行了工艺优化。优化后的工艺共五步,总收率达到43.2%。

Tert-butyl(S)-1-((R)-oxiran-2-yl)-2-phenylethylcarbamate is an important building block for preparing many HIV protease inhibitors.This research focused on optimizing the preparing process of this important intermediate.The key step for the process was to synthesize sulfoxide Ylide intermediate(3)using 1,1’-Carbonyldiimidazole(CDI)as the activating reagent by a one-pot two-steps strategy,which avoided the purification of the reactive amide intermediate(2).The process for the last two steps,reduction and epoxide formation,were also optimized.There were five steps in the improved process and the overall yield was 43.2%.