With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.3022-15-9,Piperazine-2-carboxylic acid dihydrochloride,as a common compound, the synthetic route is as follows.
CuCO3.Cu(OH)2.H2O (15.8 g) was added to the H2O (275 mL) solution of piperazine-2-carboxylic acid, dihydrochloride (22.3 g), then the mixture was refluxed and stirred for 10 min. The insoluble material was filtered off and was washed with hot H2O (165 mL). The filtrate was cooled to room temperature, and NaHCO3 (9.2 g) and 1,4-dioxane (220 mL) was added to the dark blue solution. The mixture was cooled to 0 C. and NaHCO3 (18.5 g) and 50% solution of 4-nitrobenzyl chloroformate in 1,4-dioxane (61.7 g) was added to the mixture for 0.5 h. After stirring for additional 1.5 h at 0 C., the precipitate was filtered and washed with cold H2O (140 mL), EtOH (100 mL), acetone (200 mL) and Et2O (100 mL), then it was allowed to dry under reduced pressure to obtain the pale blue crystals. The crystals were added to the 1 mol/L HCl (330 mL) solution of EDTA.2Na (20.5 g) for 30 min, and stirred for 2 h at room temperature. The suspension was filtered and the filtered material was diluted with EtOH-H2O (7:3, 550 mL) and refluxed for 10 min. The reaction mixture was filtered to obtain the colorless crystals. The recrystallization from the filtrate was carried out 3 times to obtain additional crystals. The combined crystals were dried under reduced pressure to obtain the titled compound (26.25 g, 77%) as colorless crystals. 1H NMR (D2O) delta 2.54-2.61 (m, 1H), 2.89 (dt, 2H, J=12.7, 3.4 Hz), 2.97 (br, 1H), 3.13 (br, 1H), 3.62-4.04 (m, 2H), 5.16 (s, 2H), 7.49 (d, 2H, J=8.6 Hz), 8.14 (d, 2H, J=8.6 Hz).
The synthetic route of 3022-15-9 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; Wyeth; US2006/276445; (2006); A1;,
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