Although Quantum Mechanical/Molecular Mechanics (QM/MM) methods are now routinely applied to the studies of chemical reactions in condensed phases and enzymatic reactions, they may confront technical difficulties when the reactive region is varying over time. For instance, when the solvent molecules are participating in the reaction, the exchange of water molecules between the QM and MM regions may occur on a time scale that is comparable to that of the reaction. Several adaptive QM/MM schemes have been proposed to cope with this situation. However, these methods either significantly increase the computational cost or introducing unrealistic restraints to the system. In this work, we developed a novel adaptive QM/MM scheme and applied it to a study of the nucleophilic addition reaction. In this approach, the simulation was performed with a small QM region (without solvent molecules), and the thermodynamic properties under other potential energy functions with larger QM regions (with a different number of solvent molecules and/or different level of QM theory) are computed via extrapolation using the reference-potential method. The results show that this reweighting process is numerically stable, at least for the case studied in this work. Furthermore, this method also offers an inexpensive way to examine the convergence of the QM/MM calculation with respect to the size of the QM region.