4-[5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-yl]-piperazine-1-carboxylic acid tert-butyl ester

Uses

6-(4-Boc-piperazin-1-yl)pyridine-3-boronic Acid Pinacol Ester is used as a reactant in the preparation of fluorogenic probes used to distinguish chemical warfare agents and their mimics.

Synthesis

Under nitrogen protection, 4-Boc-1-(5-bromo-2-pyridyl)piperazine (125 g, 366 mmol) was dissolved in DMF (1.30 L), and bipinacolate pinacol ester (186 g, 732 mmol), palladium acetate (4.09 g, 18.3 mmol), triphenylphosphine (19.2 g, 73.2 mmol) and potassium acetate ( 108 g, 1.10 mol). The reaction mixture was stirred at 80 °C overnight. After completion of the reaction, it was cooled to room temperature and the solid was collected by filtration. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel fast column chromatography (eluent: ethyl acetate/petroleum ether, 1:50 v/v) to afford the target product tert-butyl 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)piperidin-2-yl]piperazine-1-carboxylate (90c) as a white solid (80.0 g, yield 56%). Mass spectrum (LCMS, ESI positive ion mode): calculated value C20H32BN3O4 [M+H]+ 390.2, measured value 390.2.

References

[1] Patent: US2014/364414, 2014, A1. Location in patent: Paragraph 0945; 0950-0951
[2] Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5361 - 5379
[3] Patent: US2013/225548, 2013, A1. Location in patent: Paragraph 0531; 0632
[4] Patent: CN104650049, 2018, B. Location in patent: Paragraph 0426; 0427