论文部分内容阅读
开发了一种醛糖还原酶抑制剂(2S,4S)-6-氟-2,3-二氢-2’,5’-二氧螺(4H-1-苯并吡喃-4,4’-咪唑基)-2-酰胺化合物的新合成方法,以价格优廉的马来酰亚胺和对氟苯酚为原料,经Oxo-Michael加成反应、水解反应、手性拆分试剂(S)-α苯乙胺拆分得到高光学纯度的(S)2-(4-氟苯氧基)-1,4丁二酸,后经环化反应、布克尔反应与酰胺化反应得目标产物,总收率24%。合成过程中所有的中间体及目标产物均经比旋光度、1HNMR测定并与参考文献值比较。本方法成本低、收率较高、反应条件温和、反应环境较为友好、合成后处理操作简便并且安全,适合大规模制备。
An aldose reductase inhibitor (2S, 4S) -6-fluoro-2,3-dihydro-2 ’, 5’-dioxo spiro (4H-1-benzopyran-4,4’ -imidazolyl) -2-amide compounds, the inexpensive synthesis of maleimide and p-fluorophenol by Oxo-Michael addition reaction, hydrolysis reaction, the chiral resolving agent (S) -α-phenylethylamine to obtain (S) 2- (4-fluorophenoxy) -1,4 succinic acid with high optical purity. After the cyclization reaction, the reaction between the reaction product and the amidation reaction gave the target product , The total yield of 24%. All intermediates and target products in the synthesis process were measured by specific rotation, 1HNMR and compared with the reference value. The method has the advantages of low cost, high yield, mild reaction conditions and relatively friendly reaction environment, and the post-synthesis treatment is simple, convenient and safe and is suitable for large-scale preparation.