Background
Traditional 11C-carboxylation from [11C]CO2 is achieved by the use of either Grignard reagents or boronic ester precursors, however presenting limitations related to air and moisture sensitivity, functional group tolerance, low RCYs and reproducibility.1,2 Improvements on 11C-carboxylation could be achieved by a copper-catalysed desilylative carboxylation reaction of trialkoxysilyl and trimethylsilyl derivatives.3
Aims
The development of a novel, one-pot and widely-applicable protocol for 11C-carboxylation and 11C-methylation involving the use of trimethylsilane and trialkoxysilane derivatives to be achieved in short synthesis times, with high molar activities and RCYs.
Methods
An aryltrimethylsilane or aryltrialkoxysilane derivative is initially mixed with a fluoride source (KF-K2.2.2), a copper catalyst (CuI) and a CO2-trapping agent (BEMP). The activated precursor reacts with [11C]CO2 or [11C]CH3I to yield the [11C]aryl carboxylate or [11C]tolyl derivative, respectively. This method uses a simple one-vial, one-valve set-up.
Results and Conclusion
Six [11C]carboxylic acids were obtained from their corresponding trimethylsilyl and trialkoxysilyl precursors with RCYs up to 93% (non-isolated, estimated by radio-HPLC) within 12 minutes post [11C]CO2 delivery. 11C-methylation was achieved, as well, with a RCY of 16%. This method represents a solid alternative in the radiolabelling of [11C]carboxylic acids and [11C]methylated aromatic rings.