This work presents a methodology in order to determine the operating conditions simultaneously optimising the chemical yield and considering the safety aspect. The aim is to determine time evolutions of the reacting mixture temperature and the feed rate of reactants which not only define a maximal efficiency but also involve an adequate generated heat which can be removed by the cooling system. The problem is converted into a non-linear programming problem which is solved by standard Non Linear Programming. The methodology is validated on an industrial synthesis of a pharmaceutical product which presents high exothermicity. Results show the influence of the safety and economical constraints on the determination of optimal operating conditions. Especially, when no constraints are considered, the optimal solution is to operate batch-wise. When the generated heat is limited, the reactant has to be introduced according to a specified feed-rate profile. Experiments carried-out in a 1 litre pilot plant reactor confirm the optimisation results. This reactor is equipped with a control methodology based on temperature control through pressure which allows to remove a large amount of heat through the condenser. Then, scale-up to a 8 m(3) glass-line jacketed reactor shows the relevance of the constrained optimisation approach.