Optimization of the synthetic procedure for production of active pharmaceutical ingredient Omeprazole is presented. The properties of Omeprazole and its precursors were thoroughly explored by physicochemical investigations of the corresponding protonation and solution processes. The protonation equilibrium constants (KH) and solvation thermodynamic properties, such as solution enthalpies and entropies, as well as solubility of the starting materials and the intermediate were determined. Since the presented synthetic strategy was based on the modification of the reaction media, all measurements were performed in pure methanol and different methanol/water mixtures, which led to the selection of the solvent optimal for the Omeprazole preparation. In addition, it was proven that the conventionally used energetically demanding refluxing procedure in the first step of the Omeprazol synthesis could be avoided. It was also shown that the period of trituration employed in the step involving precipitation of the final product can be significantly reduced. All the obtained results were thoroughly discussed, and aided the conception of the new procedure for Omeprazole preparation. The improved (greener) procedure was based on the processes demanding less organic solvents, at the same time being energy- and time-more efficient. It was also proven that it could be implemented in the large scale production. This work presents a concept which could be extended to other similar systems, improving the synthetic procedures of highly used pharmaceuticals, while lowering ecological risks and production expenses.