An alkoxyacetyl group (AAc) group was found to be an efficient linker for high-throughput synthesis of small molecules on a soluble polymer support. The linker allows high-yield loading of alcohols and phenols either by conventional carbodiimide-mediated esterification or transesterification using Yb(OTf) 3. Chemoselective cleavage to release small molecules is attained also by Yb(OTf) 3 or TMSCHN 2. The preparation, protocols for loading and releasing of small molecules, and an application to the Ugi four-component coupling reaction are reported.