4-[4-(tert-Butoxycarbonyl)piperazino]benzoic acid

Uses

Boc-piperazine-benzoic acid is a PROTAC linker and can be used in the synthesis of PROTACs, such as PROTAC androgen receptor (AR) degrader ARD-2128 (HY-13229)[1].

Synthesis

General procedure for the synthesis of tert-butyl 4-(4-carboxyphenyl)piperazine-1-carboxylate from tert-butyl 4-(4-(methoxycarbonyl)phenyl)piperazine-1-carboxylate: 4-(4-(methoxycarbonyl)phenyl)piperazine-1-carboxylic acid tert-butyl ester (3.2 g, 10 mmol) was reacted with 2M NaOH solution (50 mL) in a mixture of THF (50 mL) and EtOH ( 50 mL) in a mixed solvent and the reaction was stirred at 60 °C for 3 hours. After completion of the reaction, the reaction mixture was concentrated to give a residue. The pH of the residue was adjusted to 7 with 2M HCl solution and filtered to afford tert-butyl 4-(4-carboxyphenyl)piperazine-1-carboxylate as a white solid (3.0 g, 100% yield).

References

[1] Han X, et al. Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer. J Med Chem. 2021;64(17):12831-12854.