A Synthesis of 3,5-Disubstituted Phenols

Robust and scalable syntheses of some synthetically useful 3,5-disubstituted phenols are presented. The process involves the selective displacement of a halogen by nucleophilic aromatic substitution using a preformed mixture of potassium tert-butoxide and p-methoxybenzyl alcohol (PMB−OH), followed by deprotection of the PMB ether with acid in the presence of 1,3-dimethoxybenzene. These processes have been demonstrated on kilogram scale, providing crystalline phenols in good yield and high purity.