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A safe and scalable synthesis of 2-(1,2,4-oxadiazol-3-yl)propan-2-amine hydrobromide is described. A process safety-driven synthetic strategy was employed for the selection of thermally stable compounds en route to the target 1,2,4-oxadiazole. Application of process safety principles and tools for predicting the stability of process streams, isolated compounds, and for defining optimum reaction parameters are discussed in detail. The effect of protecting groups on the thermal stability of isolated intermediates is also highlighted.