For the synthesis of this series of PROTACs, VHL ligand 20 was synthesized in two steps: a first coupling reaction of previously reported compound 19 (ref. ) with 1fluorocyclopropane-1-carboxylic acid, followed by deprotection of the thiol moiety (Scheme 4). Linkers 16a-c were connected to 20 via a sulphur alkylation reaction in the presence of DBU as the base. Deprotection of the tert-butyl ester group of 21a-c, and subsequent coupling with 3 under the same conditions described above, delivered the final compounds 22a-c in good yields (Scheme 4).