Abstract: Benchtop chemistry, a pivotal aspect of chemical synthesis, entails conducting chemical experiments and analyses on a smaller scale within a controlled laboratory environment. It encompasses the exploration of chemical properties, reactions, and compositions using relatively modest quantities of chemicals. When current benchtop chemistry workflows were examined, several bottlenecks were identified, impeding the efficiency and productivity of laboratory operations. Notably, manual sample preparation, pipetting and liquid handling, data entry and documentation, and sample tracking and labeling pose significant challenges. The National Center for Advancing Translational Sciences (NCATS) is pioneering a paradigm shift in the realm of chemistry through “A Specialized Platform for Innovative Research Exploration (ASPIRE)”. This initiative seeks to elevate the drug discovery cycle by supporting the workflow from hypothesis generation to biological testing with current focus on chemistry, in an attempt to improve it from an artisanal craft to a contemporary, information-driven science. By addressing long-standing challenges such as the lack of standardization, low reproducibility, and the inability to predict chemical behaviors, ASPIRE aims to expedite the development of novel, safe, and cost-effective treatments, thereby benefiting a larger population of patients. To overcome these hurdles, the engineering team at NCATS has devised innovative solutions, focusing on advanced robotics, process automation, labware handling optimization, software integration, and comprehensive training. Their concerted efforts target critical bottlenecks in the chemical synthesis process, namely isolation, and purification. Among the many manual bottlenecks addressed, a benchtop automated solid phase extraction (SPE) system highlights a potentially universally applicable product isolation process from chemical reactions—a process not widely applied routinely in labs today. This system streamlines solvent selection, mixing, cartridge size selection, media type, and automated fraction collection through programmatic creation and selection of methods. This allows for execution of methods tailored to the chemistry, storing crucial metadata and telemetry data associated with each run that can be used to further facilitate downstream processing as well as assess experimental success and reproducibility. When examining workflows associated with benchtop chromatographic purification, opportunities to facilitate and automate the handling of chromatography fractions were addressed. A system for concentrating all fractions of interest simultaneously to significantly reduced volumes was coupled to a second system that allowed fractions to be automatically pooled based on fraction maps pulled from the chromatography instruments. The vials are further automatically weighed and capped to afford the capture of accurate net weights of the pooled fractions. Our hope is that the demonstration of these advancements serve as transformative enhancements to benchtop chemistry workflows performed everywhere and thereby help accelerate scientific research in many areas.