Wipf Peter, Wang Xiaodong
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
J Comb Chem. 2002 Nov-Dec;4(6):656-60. doi: 10.1021/cc020041m.
A combinatorial library of oxazolines and thiazolines was synthesized in moderate to excellent yields using a newly developed methodology. Free carboxylic acids were directly condensed with amino alcohols and aminothiols in the presence of 3-nitrophenylboronic acid as a dehydration catalyst. The library synthesis illustrates the scope of this process: After traditional reaction optimization, a total of 17 oxazolines and 6 thiazolines were successfully prepared in a 24-reaction setup in a Radleys GreenHouse parallel synthesizer. The yields of the parallel reactions ranged from moderate to excellent, depending largely on carboxylate reactivity and functionalization, and generally exceeded those of the traditional reaction setup. The target compounds were isolated in high purities (average purity is 96% according to GC analysis) after passing reaction mixtures through short PrepSep SPE Florisil cartridges.
使用新开发的方法，以中等至优异的产率合成了恶唑啉和噻唑啉的组合文库。游离羧酸在3-硝基苯硼酸作为脱水催化剂的存在下，直接与氨基醇和氨基硫醇缩合。文库合成展示了该方法的适用范围：经过传统反应优化后，在Radleys GreenHouse平行合成仪中，通过24个反应设置成功制备了总共17种恶唑啉和6种噻唑啉。平行反应的产率从中等到优异不等，这在很大程度上取决于羧酸盐的反应活性和官能化情况，并且通常超过传统反应设置的产率。将反应混合物通过短的PrepSep SPE弗罗里硅土柱后，目标化合物以高纯度分离出来（根据气相色谱分析，平均纯度为96%）。
