To confirm that degradation is FEM1B dependent, we synthesized a non-degrading control of 1g, which was the most active PROTAC. The non-degrading control 1g-nc was designed to lack the electrophilic warhead and instead bears a propionyl moiety, which is known to abolish binding to FEM1B. This was realized by treating 8 with propionyl chloride to yield the corresponding tertiary amide, deprotection of the tert-butyl ester, and the subsequent amide coupling with the solid-phase bound precursor 5g (Scheme 2). After cleavage from the resin, the non-degrading control 1g-nc was generated in a purity of > 95% after purification by preparative HPLC.