Convenient preparation of 4-formyl-3,5-dimethoxyphenol and its incorporation into linkers and resins for solid-phase synthesis

4-Formyl-3,5-dimethoxyphenol (1) is a key synthetic intermediate used to pr epare the BAL family (backbone amide linker) of acid-labile linkers and res ins. The utility of these linkers and resins for solid-phase synthesis of b oth peptides and non-peptides has been amply demonstrated. In this article we report a simple and scalable procedure for preparation of isomerically p ure 4-formyl-3,5-dimethoxyphenol (1) and its subsequent incorporation into a representative BAL linker and functionalized resin: 4-(4-formyl-3,5-dimet hoxyphenoxy)-butanoic acid and 4-formyl-3,5-dimethoxyphenoxy-polystyrene re spectively. The procedures are reproducible, are readily scalable, and requ ire no chromatography.