The conformational inversion rates of calix[4]arene and p-tert-butyl-calix[4]arene in a vacuum and in chloroform have been calculated by using molecular dynamics simulations, as a model study for a process with a pronounced solvent effect. The reaction of p-tert-butyl-calix[4]arene in chloroform is complicated by the ability of one of its conformations to capture a chloroform molecule in its cavity, while the smaller cavity of the calix[4]arene is too small for an inclusion. The relatively easily obtained free energies of conformational inversion in a vacuum prove to be a great asset in the calculations with calix[4]arene in chloroform. But they are of limited use for p-tert-butyl-calix[4]arene in chloroform, where we had to resort to more advanced methods, to wit, window sampling and a combined coupling parameter-umbrella sampling approach. Conformational inversion rates calculated by the reactive flux method are in good agreement with experimental data.