Godfrey Jollie D, Fox Rita T, Buono Frederic G, Gougoutas Jack Z, Malley Mary F
Department of Process Research and Development, Pharmaceutical Research Institute, Bristol-Myers Squibb, Post Office Box 4000, Princeton, New Jersey 08543-4000, USA.
J Org Chem. 2006 Oct 27;71(22):8647-50. doi: 10.1021/jo0613380.
Conversion of an alpha,alpha-dichloroester to the corresponding alpha-keto acid was unexpectedly complicated by a novel 1,4-homofragmentation. Investigation of the kinetics of this reaction revealed a mechanism involving an alpha-lactone intermediate, which can lead to both the desired alpha-keto acid and the 1,4-homofragmentation, with the product distribution being dependent upon reaction conditions. This information allowed development of a process that affords the alpha-keto acid exclusively and should be generally applicable to the preparation of alpha-keto acids from alpha,alpha-dichloroesters or acids.
α,α-二氯酯向相应的α-酮酸的转化意外地因一种新型的1,4-同系碎片化反应而变得复杂。对该反应动力学的研究揭示了一种涉及α-内酯中间体的机制，该中间体可生成所需的α-酮酸和发生1,4-同系碎片化反应，产物分布取决于反应条件。这些信息使得能够开发出一种仅生成α-酮酸的方法，并且该方法通常应适用于由α,α-二氯酯或酸制备α-酮酸。
