Methanol → {2-[(2,2-Dimethyl-[1,3]dioxolan-4-ylmethyl)-amino]-propyl}-carbamic acid tert-butyl ester

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The commercially available Tert-butyl-N-(2-hydroxypropyl)carbamate (10 g, 57.0 mmol)) and trietylamine (12 ml, 85.6 mmol) were dissolved in dichloromethane (60 mL) and cooled to 0° C. Methanesulfonyl chloride (4.9 ml, 62.7 mmol) was added dropwise to the ice-cold solution and the reaction was allowed to warm up to room temperature with stirring overnight. The reaction was then quenched with NaOH (1M, 5 ml). The organics were washed with water (2×100 ml) and then brine, collected, dried over MgSO4, filtered and evaporated under reduced pressure to give methanesulfonic acid 3-tert-butoxycarbonylamino-propyl ester (13.5 g). The crude methanesulfonic acid 3-tert-butoxycarbonylamino-propyl ester (13.5 g, 53 mmol) and 2,2-dimethyl-1,3-dioxolane-4-methanamine (12 g, 91.6 mmol) were stirred overnight at room temperature. The mixture was dissolved in ethyl acetate (100 ml) and washed with water (3×100 ml) and brine. The organics were collected, dried over MgSO4, filtered and evaporated under reduced pressure to give an oil. This was purified by silica column chromatography eluting with ethyl acetate: methanol to give the desired product {2-[(2,2-Dimethyl-[1,3]dioxolan-4-ylmethyl)-amino]-propyl}-carbamic acid tert-butyl ester (4.74 g, 17.3 mmol). Mass Spec (ESI) m/z: [M+H]+=289.12. 1H NMR (CDCl3; 300 MHz) δ=5.15 (s, br, 1H), 4.19 (quin, 1H), 4.02 (t, 1H), 3.66 (t, 1H), 3.18 (q, 2H), 2.70 (m, 4H), 1.63 (quin, 2H), 1.42 (s, 9H), 1.40 (s, 3H), 1.40 (s, 3H). 13C NMR (CDCl3; 300 MHz) δ=156.00, 109.05, 78.85, 75.23, 67.47, 52.30, 47.91, 39.20, 29.69, 28.35, 26.81, 25.37.

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