To test conditions for this radiofluorination reaction, 12 substrates are selected initially which cover a range of functional groups and which have previously delivered a variety of radiochemical conversions from 1–75%. This allows the HTE workflow and analysis methods to be assessed across both high- and low-performing substrates. Additionally, conditions including and excluding both pyridine and nBuOH additives are tested as they are known to enhance yields of this reaction for some substrates, and each set of conditions is run twice for reproducibility, thereby providing 96 reactions to fill a 96-well plate. Importantly, the reactions are carried out on a smaller scale than most manual radiochemical reactions, using 2.5 μmol of the (hetero)aryl pinacol boronate ester substrate. A copper triflate (Cu(OTf)2) catalyst, [18F]KF salt and dimethylacetamide (DMA) solvent are also used.
A 96-well plate-based solid-phase extraction, followed by the use of either autoradiography, gamma scintillation counters or positron emission tomography scanners, allows rapid analysis and determination of the radiochemical conversions of these reactions. Interestingly, the use of autoradiography for HTE appears less reliable for radiochemical conversion determination than the other analytical methods tested.
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