To a solution of N-Boc-ethylenediamine (5.0 g, 31.2 mmol, 1.0 equiv, 1-2) in diethyl ether (30 mL) was added 3-methyl-3-butene-2-one (2.6 g, 31.2 mmol, 1.0 equiv, 1-1) and the reaction was stirred at room temperature for 18 hours. The reaction mixture was then cooled to 0° C. and triethylamine (6.5 mL, 46.8 mmol, 1.5 equiv) and benzyl chloroformate (5.4 mL, 37.4 mmol, 1.2 equiv) were added. The reaction mixture was stirred a further 12 h and partitioned between EtOAc and a 10% aqueous citric acid solution. The layers were separated and the organic was washed with 5% aqueous Na2CO3, then with brine, dried over Na2SO4 and concentrated by rotary evaporation. The residue was dissolved in dioxane (50 mL) and treated with a solution of 4N HCl in dioxane (70 mL, ca. 10 equiv) and the reaction mixture was stirred for 2 h at ambient temperature. The reaction mixture was concentrated directly, dissolved in 1N HCl (100 mL) and extracted with diethyl ether. The aqueous was neutralized with 1N NaOH (150 mL) and subsequently extracted with 3:1 chloroform:ethanol (3×200 mL), dried over MgSO4 and concentrated. The resulting residue was dissolved in DCM (100 mL) and glacial acetic acid (2 mL) was added. After 30 minutes, NaBH(OAc)3 (6.4 g, 30.2 mmol) was added and the reaction was stirred for 1 h. The reaction mixture was concentrated directly; partitioned between saturated NaHCO3 (50 mL) and 3:1 chloroform:ethanol (150 mL) The aqueous layer was extracted with chloroform:ethanol (2×150 mL), dried over MgSO4 and concentrated. The residue was dissolved in DCM (100 mL) and to the solution was added triethylamine (4.2 mL, 30.2 mmol) and Boc2O (5.0 g, 22.7 mmol) and the reaction mixture was stirred 18 hours. To the reaction mixture was added a 10% aqueous citric acid solution. The organic phase was dried over MgSO4 and concentrated. The residue was purified by column chromatography on silica gel (0 to 75% EtOAc in hexanes) to provide 1-3 as an oil. Data for 1-3: LC/MS: m/z (M+Na)=385.2 found; 385.5 required.
