In this work, we propose a cost-effective protocol for the calculation of rate constants within the framework of multiconformer transition state theory. We have developed this methodology while calculating for the first time on a theoretical level rate constants for a series of six reactions between the OH radical and hydrofluoropolyethers: the latter are promising third-generation CFC replacements whose atmospheric impact is still widely unknown. Our investigation, which is based on computationally accessible M08-HX/apcseg-2//M08-HX/pcseg-1 calculations, shows that two of our rate constants are within a factor of 0.6 and 1.4 of experimental data, a good result that probably benefits from some error cancellation. It also exhibits a reactivity trend, for which we provide detailed insights that could be used to shed new light on the general reactivity of ethers toward OH. Finally, because the studied reactions share a ubiquitous mechanism in atmospheric chemistry, we hope that our protocol can be routinely applied to explore the reactivity of computationally challenging reactions and to pave new ways in the development of greener CFC replacements.