Synthesis
To a solution of ethylenediamine (7.70 g, 128 mmol) in toluene (55 mL) was added slowly and dropwise a solution of ethyl 2-bromo-2-methylpropionate (5.00 g, 25.6 mmol) in toluene (5 mL). The reaction mixture was stirred at room temperature for 1 hour and then warmed up to reflux and continued stirring for 16 hours. Upon completion of the reaction, the mixture was extracted with toluene (30 mL). The organic layer was separated and dried with anhydrous Na2SO4 and subsequently concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (100-200 mesh, eluent DCM solution containing 2% to 10% ammonia in methanol) to afford 3,3-dimethylpiperazin-2-one (2.81 g, 87% yield) as an off-white solid.LC/MS (ESI) analysis: m/e [M+H]+ 128.90, retention time 0.61 min, purity 69.8%. 1H NMR (400 MHz, DMSO-d6) δ 1.15 (s, 6H), 2.24 (s, 1H), 2.80-2.86 (m, 2H), 3.10-3.16 (m, 2H), 7.35 (s, 1H).
References
[1] Patent: WO2017/20010, 2017, A1. Location in patent: Paragraph 0128
[2] Patent: WO2015/38417, 2015, A1. Location in patent: Page/Page column 113
[3] Tetrahedron Letters, 1994, vol. 35, # 51, p. 9545 - 9548
[4] Patent: WO2005/16900, 2005, A1. Location in patent: Page/Page column 27
[5] Patent: WO2006/86986, 2006, A1. Location in patent: Page/Page column 14-15
