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Abstract：
The 2,2,2-trifluoroethoxy group increasingly features in drugs and potential tracers for biomedical imaging with positron emission tomography (PET). Herein, we describe a rapid and transition metal-free conversion of fluoroform with paraformaldehyde into highly reactive potassium 2,2,2-trifluoroethoxide (CF3CH2OK) and demonstrate robust applications of this synthon in one-pot, two-stage 2,2,2-trifluoroethoxylations of both aromatic and aliphatic precursors. Moreover, we show that these transformations translate easily to fluoroform that has been labeled with either carbon-11 (t1/2 = 20.4 min) or fluorine-18 (t1/2 = 109.8 min), so allowing the appendage of complex molecules with a no-carrier-added 11C- or 18F- 2,2,2-trifluoroethoxy group. This provides scope to create candidate PET tracers with radioactive and metabolically stable 2,2,2-trifluoroethoxy moieties. We also exemplify syntheses of isotopologues of potassium 2,2,2-trifluoroethoxide and show their utility for stable isotopic labeling which can be of further benefit for drug discovery and development.
摘要：
2,2,2-三氟乙氧基在正电子发射断层扫描（PET）生物医学成像的药物和潜在示踪剂中的特征越来越多。在这里，我们描述了一种快速且无过渡金属的含氟形式与多聚甲醛转化为高反应性钾2,2,2-三氟乙醇（CF3CH2OK），并证明了这种合成子在一锅中的强大应用，芳族和脂族前体的两阶段2,2,2-三氟乙氧基化。此外，我们表明，这些转化很容易转化为已经标记有碳11（t1/2=20.4分钟）或氟18（t1/2=109.8分钟）的氟形式，因此允许具有未添加载体的11C-或18F-2,2,2-三氟乙氧基的复杂分子的附属物。这提供了产生具有放射性和代谢稳定的2,2,2-三氟乙氧基部分的候选PET示踪剂的范围。我们还举例说明了2,2,2-三氟乙氧基钾的同位素体的合成，并显示了它们用于稳定同位素标记的用途，这可能对药物的发现和开发有进一步的好处。
