Monoethyl malonate → Tert-butyl 4-(3-ethoxy-3-oxopropanoyl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

HOBt (3.48 g, 25.8 mmol) and DIPEA (6.94 g, 53.8 mmol) were added to a stirred solution of malonic acid monoethyl ester (2.84 g, 21.5 mmol) in DMF (10 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (4.95 g, 25.8 mmol) followed by piperazine-1-carboxylic acid tert-butyl ester (4 g, 21.5 mmol) were added. The reaction mixture was stirred at room temperature overnight then diluted with water. The product was extracted with ethyl acetate and the ethyl acetate was washed with brine solution, dried over Na2SO4 and concentrated to afford 5.2 g (84%) of 4-(2-ethoxycarbonyl-acetyl)-piperazine-1-carboxylic acid tert-butyl ester. LCMS: 301.17 (M+1)+ 84.5%. 1H NMR: (CDCl3): δ 4.0 (q, 2H), 3.45 (m, 2H), 3.3 (m, 8H), 1.25 (s, 9H), 1.1 (t, 3H).

Provenance & Evidence