With the advent of new technologies in organic chemistry, innovative synthetic methodologies have been developed across the years, providing sustainable alternatives to the traditional transformations. In particular, the employment of sustainable electrochemical reactions have impacted the way of conceiving redox processes, dramatically improving the atom-economy and the safety of the reactions by avoiding the involvement of dangerous oxidants or reductants. Furthermore, electrochemical and photochemical transformations express their scalable potential in combination with flow technology, indicating the feasibility of these methods across a broad scale regime. 10 Intrigued by the possibility of providing versatile tools to the pharmaceutical industry that combine modularity and scalability features, we identified relevant APIs that would benefit from this exploration. Among these compounds delamanid was found to be of interest both for its application and molecular characteristics. This API has been prescribed for multidrug-resistant tuberculosis treatment and appeared in the World Health Organization's List of Essential Medicines in 2014. From a synthetic point of view, the aryl ether piperidine core attracted our attention as a critical fragment of the molecule for its functional groups handles, which allowed the linkage of different portions of the scaffold. The patent synthetic protocol reported that the protected 4-hydroxy piperidine was subjected to mesylation under cryogenic conditions, followed by nucleophilic substitution on the 4-trifluoromethoxy phenol under basic conditions at high temperatures and final deprotection under reflux conditions. This three-step sequence is considered a non-atom economical and harsh way to access the key intermediate 1. In this work, the robust, scalable, and sustainable synthesis of this system employing a Ni-electrocatalyzed etherification is presented, providing a valuable example of conciliation between high versatility and robustness across different scale regimes thanks to an electrochemical flow reactor. We commenced our investigation by establishing the appropriate coupling conditions for our designated substrates, 4-trifluoromethoxy bromobenzene (2a) and 4hydroxy N-Boc piperidine (3a, Figure ). The conditions reported by Baran and collaborators for nickel electrocatalyzed C-O bond formation were identified as a valid starting point for the synthesis of compound 4a. Indeed, as the replication of the electrochemical protocol led to the formation of the product in good yield (Entry 1, 48%), we sought to further explore this reaction in order to facilitate the experimental protocol, bearing in mind the importance of the late-stage scale-up phase. The first important experimental detail that emerged from the reaction survey was the importance of pre-stirring the reaction mixture. As reported in the original protocol, the agitation of the reaction mixture for 10 minutes prior to electrolysis improved the formation of the product. However, we found an extended time or 30 minutes pre-stirring more beneficial and reproducible with these coupling partners (Entry 2-3). Upon deeper study of this observation, it was noticed that this induction phase was extremely beneficial in the release of one ligand unit from the precatalyst, indicating that this activation is essential for the success of the reaction (see Supporting Information for further details). Next, we evaluated the electrode material (Entry 4-6). In this case, the use of Reticulate Vitreous Carbon (RVC) both as cathode and anode in the electrochemical cell provided better results compared to all the other combinations tested (Entry 6, 62%). Other modifications such as solvent, base, and ligand screenings showed lower performances (Entry 7-9). To further assess the characteristics of the reaction, moisture sensitivity tests were carried out (Entry 10-11). The addition of water resulted in a much lower yield, as suggested by the need of molecular sieves in the original protocol, while the reaction could be carried out open to air with only a slight decrease of performance. Finally, the necessity of electricity and an appropriate catalytic system was confirmed via control experiments. Surprisingly, when the same substrates were subjected to the state-of-the-art photochemical conditions for the synthesis of C-O bonds employing metallaphotoredox approach, employing 4CzIPN as photocatalyst with NiBr2•dme under 465 nm light irradiation, only traces of products could be observed, showing the complementarity between photochemical and electrochemical systems (see Supporting Information for further details). The optimized electrochemical reaction conditions involved, along with the aryl halide and 3 equivalents of the alcohol, 10 mol% of Ni(dttbbpy)3Cl2, 2 equivalents of DBU, 0.2 M of tetrabutylammonium bromide as supporting electrolyte and N,Ndimethyl acetamide (DMA) as solvent. This stock solution, after 30 minutes of pre-stirring, was subjected to 10 mA of constant current until 6.0 F/mol of charge had been passed through the solution in a cell equipped with RVC electrodes as both cathode and anode.