An efficient synthesis of a dual PPAR α/γ agonist and the formation of a sterically congested α-aryloxyisobutyric acid via a Bargellini reaction
An efficient synthesis of a dual PPAR α/γ agonist and the formation of a sterically congested α-aryloxyisobutyric acid via a Bargellini reaction
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DOI：
10.1021/jo051027
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发表时间：
2005-10-14
影响因子：
3.6
通讯作者：
Zhou, G
中科院分区：
文献类型：
--
作者：
Cvetovich, RJ;Chung, JYL;Zhou, G
研究了苯并异恶唑1的合成及其与1，1，1-三氯-2-甲基-2-丙醇（藜芦酮）反应生成α-芳氧基异丁酸2的方法。苯并异恶唑I通过甲磺酰氯/碱与中间体肟8或亚硫酰氯/碱的作用以高产率形成，亚硫酰氯/碱最初形成环状亚硫酸盐10。一个高度反应性的，短寿命的中间体来自于藜芦酮检测ReacIR和其半衰期确定为类似于5分钟。Bargellini反应的反应条件进行了开发，导致在95%的产率2从反应的高度受阻酚1与藜芦酮半水合物和粉状氢氧化钠在丙酮中。因此，高度受阻的α-芳氧基异丁酸可以在单一步骤中以高产率制备。
A practical synthesis of benzisoxazole 1 and its conversion to alpha-aryloxyisobutyric acid 2 using 1,1,1-trichloro-2-methyl-2-propanol (chloretone) was developed. Benzisoxazole I was formed in high yields by the action of either methanesulfonyl chloride/base upon intermediate oxime 8 or with thionyl chloride/base, which initially forms cyclic sulfite 10. A highly reactive, short-lived intermediate derived from chloretone was detected by ReacIR and its half-life determined to be similar to 5 min. Reaction conditions for the Bargellini reaction were developed that resulted in a 95% yield of 2 from the reaction of highly hindered phenol 1 with chloretone hemihydrate and powdered NaOH in acetone. Thus highly hindered alpha-aryloxyisobutyric acids can be made in a single step in high yield.