The Passerini three-component reaction (Passerini-3CR) has been studied via on-line microreactor/electrospray ionisation mass spectrometry (MRT/ESI-MS) reaction monitoring to demonstrate the high-throughput screening potential of continuous microreactors for macromolecular design. The Passerini-3CR is an efficient reaction, but generally requires some reagents in excess and comparatively long reaction times to complete. Herein, a reaction protocol is proposed for high yields within minutes of reaction time at equimolar reactant concentrations. The Passerini-3CR allows for the synthesis of α-acyloxy carboxamides by combining an aldehyde (or ketone), an isocyanide and a carboxylic acid moiety. A carboxylic acid (i, 1300 g mol-1) and aldehyde (ii, 1150 g mol-1) endgroup functionalized low molecular weight poly(n-butyl acrylate) were separately screened with their corresponding components as follows: (i) with dodecylaldehyde and ethylisocyano acetate and (II) with acetic acid and ethylisocyano acetate. Screened parameters were molarity ratios, residence times, absolute reagent concentrations and reactor temperatures. Equimolar carboxylic acid/aldehyde concentrations give excellent Passerini product yields (>95%) within 10 minutes of reaction time. The established reaction protocol is then transferred to a conventional batch process for the synthesis of diblock copolymers P(nBA)-b-P(nBA), P(nBA)-b-P(MMA) and P(nBA)-b-P(EGMEA) with variable block lengths. All diblock copolymers are synthesized by using equimolar carboxylic acid/aldehyde polymer mixtures, showing excellent coupling efficiencies in size exclusion chromatography analysis. The isocyanide component, being ethylisocyano acetate, is consistently utilized in excess in agreement with the literature.