Experimental setup and reaction conditions are shown in Figure . A solution of 1,4-benzenedimethanol (1) (0.20 M) and Et 3 N (0.20 M) in MeCN and a solution of DMAP (0.10 M) in MeCN were injected into a PTFE T-shape mixer (inner diameter: 0.5 mm) using syringe pumps. The resultant mixture was passed through the reaction tube (volume: 0.50 mL, Vapourtec R-Series Tubing Kit). The resultant mixture and a solution of acetic anhydride (2) (0.20 M) and biphenyl (0.0020 M) in MeCN were injected into the second PTFE T-shape mixer (inner diameter: 0.5 mm). The resultant mixture was passed through reaction tube 2 at (volume: 4.0 mL, Vapourtec R-Series Tubing Kit). Reaction tubes 1 and 2 and two T-shape mixers were immersed in a water bath with a temperature control. Syringe pumps in the system were from TriContinent and controlled by lab automation software Flab. The resultant mixture was added into saturated NH 4 Cl solution and CH 3 OH at room temperature. Yields of 4-hydroxymethylbenzyl acetate (3) were determined by HPLC-UV analysis. More details can be found in Appendix A. Four reaction variables were identified that are important for this reaction and were selected, also shown in Figure . Namely, equivalent of 1,4-benzenedimethanol (1):acetic anhydride (2), DMAP (catalyst) loading, flow rate of acetic anhydride (2) and temperature. Table summarized the range of each variable. The flow rate of 2 was set to be Z mL/min, ranging from 0.50 mL/min to 2.00 mL/min. The equivalent of 1:2 was changed by adjusting the flow rates X in a range of 10.00-0.50 mL/min; catalyst loading was changed by adjusting the flow rates Y in a range of 0.05-2.00 mL/min. The reaction tube 1 and 2 was kept in a water bath with a temperature of W °C. The same objective functions as in silico study -maximizing space-time-yield and minimizing E-factor, were chosen as the objectives for optimizing this reaction.