Abstract The residue curve mapping technique (RCM) has been considered a powerful tool for the flow-sheet development and preliminary design of conventional multi-component separation processes. It does not only represent a good approximation to actual equilibrium behavior, but also it allows performing feasibility analysis of separation processes where non-ideal and azeotropic mixtures are involved (Malone and Doherty, 2000). Applications of RCM to reactive distillation processes have recently been reported, but a generalized and systematic approach is still missing for reactive feeds outside the conventional composition ranges and represents the aim of this contribution. An RCM-based feasibility analysis has been applied to the synthesis of methyl tertbutyl ether (MTBE) at 11 atm and in the presence of an inert component. The reaction space, defined in terms of transformed composition, variables, has been divided into sub-regions characterized by separation boundaries. A feasibility analysis of the reactive distillation process has been performed based upon the location of the reacting mixture in the space and initial separation sequences have been generated according to the feed transformed-composition. In all the cases, high purity MTBE has been obtained as a product.