Bao Li, Fenglei Xie, Rui Zhang, Yaoyi Wang, Vijaya B. Gondi, Christopher R. H. Hale
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引用次数: 0
Abstract
A one-pot synthesis of functionalized N-trifluoromethyl pyrazoles from readily available di-Boc trifluoromethylhydrazine and dialdehydes, diketones, carbonylnitriles, and ketoesters/amides/acids is described. 19F NMR studies were used to characterize the stability of trifluoromethylhydrazine HCl salt in solution and in solid form and identified a short solution-state half-life of ∼6 h. Optimization of cyclization conditions identified DCM, combined with a strong acid, as a key to suppress the undesired des-CF3 side products, which formed as a result of the instability of trifluoromethylhydrazine and related intermediates. Despite the short-lived nature of these transient intermediates, their reactivity could be utilized to directly deliver a diverse array of pharmaceutically relevant N-trifluoromethyl pyrazoles in synthetically useful yields.
期刊介绍:
The Journal of Organic Chemistry welcomes original contributions of fundamental research in all branches of the theory and practice of organic chemistry. In selecting manuscripts for publication, the editors place emphasis on the quality and novelty of the work, as well as the breadth of interest to the organic chemistry community.