Synthesis
General procedure for the synthesis of tert-butyl 4-(4-nitrophenyl)piperazine-1-carboxylate from 4-nitrobenzyl bromide and N-BOC-piperazine: Potassium carbonate (3 g) was added to a solution containing tert-butyl 1-piperazinecarboxylate (0.74 g, 4 mmol) and 4-nitrobenzyl bromide (0.86 g, 4 mmol) in N,N-dimethylformamide (DMF, 5 mL). The reaction mixture was stirred at room temperature for 4 hours. After the reaction was completed, the product was extracted with ethyl acetate (50 mL) and the organic phase was washed with water (20 mL x 3). The organic layer was dried with anhydrous sodium sulfate and subsequently concentrated under reduced pressure to remove the solvent. The crude product was purified by column chromatography using ethyl acetate as eluent to afford the target compound tert-butyl 4-(4-nitrobenzyl)-1-piperazinecarboxylate (3) (1.22 g, 95% yield) with a melting point of 99-100 °C. 1H NMR (DMSO-d6) data were as follows: δ 8.21-8.19 (d, 2H, J = 8.8 Hz, Ar-H), 7.61 -7.59 (d, 2H, J = 8.0 Hz, Ar-H), 3.63 (s, 2H, CH2), 3.34-3.30 (m, 4H, partially fuzzy, 2 × CH2), 2.35-2.32 (m, 4H, 2 × CH2), 1.39 (s, 9H, 3 × CH3). Elemental analysis (C16H23N3O4) results are consistent with calculated values.
References
[1] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 19, p. 5592 - 5599
[2] Patent: US2004/34033, 2004, A1. Location in patent: Page/Page column 12; Sheet 1
[3] Patent: US2007/249649, 2007, A1. Location in patent: Page/Page column 116
[4] Patent: WO2012/110773, 2012, A1. Location in patent: Page/Page column 120
[5] Patent: WO2014/27199, 2014, A1. Location in patent: Page/Page column 122
