Copper-mediated nucleophilic radiofluorination using boronic precursors is a promising, general method to label aromatic compounds with [18F]fluoride. However, in various reports large amounts of precursor (60 μmol) were needed to achieve high radiochemical conversions (RCCs), which is neither ideal nor practical for the preparation of 18F radiopharmaceuticals. To investigate this matter, we studied alcohol-enhanced Cu-mediated nucleophilic radiofluorination using a variety of model reactions in which we varied the concentration of [18F]fluoride (no carrier added or isotope diluted) and the amount of precursor, base and Cu (OTF)2(Py)4. We found that lower amounts of precursors (e.g. 15 μmol) could be used, and that the amount of base (e.g., K2CO3 or KHCO3) played a critical and limiting role in the labeling reactions. Greater than one-equivalent of base and sufficient amounts of precursors and Cu (OTf)2(Py)4 were required to achieve good to high RCCs. The RCCs were also dependent on the overall concentration of the labeling reactions, with low reaction volumes and high concentrations of reagents being preferred. Our findings will help to improve the design of radiolabeling protocols using alcohol-enhanced copper-mediated radiofluorination of boronic precursors for the preparation of 18F labeled radiopharmaceuticals and other radiohalogen-labeled compounds.