Synthesis
Example 1 Preparation of 1-benzyl-4-(4-nitrophenyl)piperazine: 1-benzylpiperazine (8.81 g, 50.0 mmol), 4-fluoronitrobenzene (5.31 mL, 50.0 mmol), and potassium carbonate (6.90 g, 50.0 mmol) were dissolved in ethanol, heated to reflux temperature, and stirred for 18 hours, under nitrogen protection. After completion of the reaction, it was cooled to room temperature, the reaction mixture was diluted with water and extracted with dichloromethane. The organic phases were combined, dried with anhydrous magnesium sulfate and concentrated under reduced pressure to give a solid residue. The solid was ground with a 20:80 solvent mixture of ethyl acetate-hexane and filtered. The filter cake was air dried to give the title compound 1-benzyl-4-(4-nitrophenyl)piperazine as orange crystals in a yield of 8.45 g (57% yield) with a melting point of 218-219°C. The structure of the product was confirmed by nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis.
References
[1] British Journal of Pharmacology, 2018, vol. 175, # 12, p. 2399 - 2413
[2] European Journal of Organic Chemistry, 2001, # 16, p. 3105 - 3118
[3] Journal of Medicinal Chemistry, 2005, vol. 48, # 26, p. 8261 - 8269
[4] Patent: WO2005/7625, 2005, A2. Location in patent: Page 61
[5] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 5, p. 1092 - 1099
