To synthesize reversible covalent PROTACs, we prepared PEG-monotosylates of different lengths and coupled them to 4-OH-thalidomide to generate thalidomide-PEG-OH constructs (Supplementary Material). These were oxidized to aldehydes, followed by an aldol condensation with the BTK inhibitor cyanoacetate to generate the cyanoacrylates. During the condensation, the ether linkage nearest the cyanoacrylate in RC-1 and RC0a-j was frequently cleaved and higher molecular adducts were formed, as observed by LC/MS measurements. In the synthesis of RC-2 and RC-3 (where the last ether linkage was replaced with a CH2 group or C(CH3)2), the condensation was considerably slower with reduced unwanted side reactions and higher yield (see Supplementary Material for synthesis procedures). 1 H and C NMR spectra were recorded on a 11.7T Bruker AVANCE III HD spectrometers. Chemical shifts are reported in ppm on the δ scale downfield from TMS and are calibrated according to the deuterated solvents (see supplementary material).