This work studies the fast coupling reaction of polymers with a water competition under confined impinging jet (CIJ) mixing. The coupling reaction between polystyrene acyl chloride (PS-COCl) and polyethylene glycol amine (PEG-NH2) is used either with or without a water competition. The reactions are implemented either in a molecular homogeneous and perfect mixing or in a CIJ mixing reactor. The simulations reveal that although the process with Re-j = 1770 is mixing limited (tau(rxn1) (similar to 1.8 ms) < tau(rxn2) (similar to 7.4 ms) < tau(mix) (similar to 8.5 ms)), the desired coupling conversion (16%) and selectivity (0.17) is approaching to 18% and 0.19 respectively, which were their maxima occurred in a molecular homogeneous and perfect mixing. The simulation results successfully rationalize the low coupling conversion of about 17% reported in a previous experiment. Moreover, this study provides guidance to improve the desired conversion by increasing either [PEG-NH2](0)/[PS-COCl](0) or k(2)/k(1), which is crucial for the in-situ reactive flash nanoprecipitation (RFNP) to generate stable nanoparticles, especially with a higher drug load and less reactive polymers. The successful acquisition of the time scales of the competing reactions and mixing would be beneficial to revealing the mechanism and process of particle formation and evolution in the RFNP, where time scales of chemical reactions, mixing, and precipitation would compete to each other.