Photocatalyzed radiosynthesis of ¹¹C-phenylacetic acids

Fast and straightforward incorporation of radionuclides into pharmaceutically relevant molecules is one of the main barriers to preclinical and clinical tracer research. Late-stage direct incorporation of cyclotron-produced [C-11]CO2 to afford carbon-11-labeled radiopharmaceuticals has the potential to provide ready-to-inject positron emission tomography agents in less than an hour. The present work describes photocatalyzed carboxylation of alkylbenzene derivatives to afford C-11-phenylacetic acids. Reaction conditions and scope are investigated followed by application of this methodology to the preparative radiosynthesis of [C-11]fenoprofen, a nonsteroidal anti-inflammatory drug.