1,1'-Carbonyldiimidazole → 4-((tert-Butoxycarbonyl)amino)-3-oxobutanoic acid ethyl ester

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Reaction Conditions

Reaction Steps

Referenced: J. Med. Chem. 2008, 51 (3), 487-501. At RT, 1,1′-carbonyldiimidazole (13.88 g, 86 mmol) was added to a solution of N-Boc-glycine (Sigma-Aldrich Chemical Company, Inc.) (10.00 g, 57.1 mmol) in THF (200 mL) and the mixture was stirred for 3 h. Magnesium chloride (10.87 g, 114 mmol) and potassium ethyl malonate (Sigma-Aldrich Chemical Company, Inc.) (19.43 g, 114 mmol) were added and the resulting suspension was heated in an oil bath at 50° C. for 18 h. The reaction mixture was concentrated under reduced pressure. The off-white residue was treated with EtOAc (300 mL), then washed sequentially with 5% sodium bisulfate (2×25 mL), saturated NaHCO3 (2×50 mL), and brine (25 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The crude material was purified by chromatography through a Thomson Single Step pre-packed silica gel column (160 g, eluted with a gradient of 0-75% EtOAc in hexanes) to provide ethyl 4-((tert-butoxycarbonyl)amino)-3-oxobutanoate (10.33 g, 42.1 mmol, 74% yield) as a colorless viscous oil after drying under vacuum overnight. 1H NMR (400 MHz, CDCl3) δ ppm 5.16 (1H, d, J=5.7 Hz), 4.21 (2H, m), 4.08-4.16 (2H, m), 3.48 (2H, s), 1.45 (9H, s), 1.29 (3H, m). m/z (ESI, +ve) 268.0 (M+Na)+.

Provenance & Evidence