Synthesis
Step a: Synthesis of tert-butyl 4-(2-cyano-4-nitrophenyl)piperazine-1-carboxylate; To a solution of DMF (50 mL) containing N-BOC-piperazine (5.61 g, 30.1 mmol) and potassium carbonate (4.2 g, 30.1 mmol) was slowly added 2-fluoro-5-nitrobenzonitrile (5.0 g, 30.1 mmol). The reaction mixture was stirred at 50°C for 2 hours. Upon completion of the reaction, the mixture was poured into water, the resulting precipitate was collected by filtration and washed with water. After drying under high vacuum, tert-butyl 4-(2-cyano-4-nitrophenyl)piperazine-1-carboxylate (8.66 g, 86.6% yield) was obtained as a yellow solid, which could be used in the subsequent reaction without further purification.LC/MS analysis: retention time 6.22 min, detected as m/z 274.2 [M+H+CH3CN-Boc]+.
References
[1] Patent: US2009/99199, 2009, A1. Location in patent: Page/Page column 17-18
[2] Patent: WO2008/141976, 2008, A1. Location in patent: Page/Page column 49
[3] Patent: WO2009/79597, 2009, A1. Location in patent: Page/Page column 62-63; 152
[4] Patent: WO2005/54238, 2005, A1. Location in patent: Page/Page column 92
[5] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 18, p. 5552 - 5556
