Abstract Selective oxidation of 5‐(hydroxymethyl)furfural (HMF) to 2,5‐diformylfuran (DFF) is an important approach for biobased compound valorization through biorefinery. As there is no large‐scale process for this application yet, it is of high importance to find a suitable catalyst system for the production of DFF. In this work, we show that an important step in this direction was taken with a 5 % Ru/Al 2 O 3 catalyst, whereby essentially quantitative selectivities could be obtained in the solvent toluene without the significant formation of over‐oxidation products. A design of experiments approach was used to determine important information about the main process parameters – catalyst amount, oxygen pressure and reaction temperature. By developing an optimised washing method, excellent results were achieved in terms of catalyst reusability, with HMF conversions of over 99.5 % without loss of the catalyst‘s high selectivity after five cycles. Upscaling experiments were performed with the catalyst in a 5‐L reactor at different reactor fill rates, where complete conversion of HMF to DFF was achieved, with a 25 % longer reaction time to achieve full conversion compared to a smaller scale reactor setup.