The difluoromethylation of methyl 4-hydroxy-3-iodobenzoate has been demonstrated on multikilogram scale. Prior to execution, several issues had to be addressed. First, the difluorocarbene source had to be explored to avoid using highly toxic gases such as chlorodifluoromethane. After choosing sodium chlorodifluoroacetate as the difluororcarbene precursor and potassium carbonate as the base, a safety evaluation had to be performed ...
