Synthesis
Step d: Synthesis of tert-butyl (S)-2-(2-aminoethyl)pyrrolidine-1-carboxylate. The product of step c, tert-butyl (S)-2-(cyanomethyl)pyrrolidine-1-carboxylate (1.45 g, 6.9 mmol) was suspended in ammonia saturated methanol (50 ml) and Raney-Nickel (ca. 1.0 g) and hexachloroplatinic acid (IV) hydrate (80 mg dissolved in 1 ml of water) were added. The mixture was placed in a Parr reaction flask and stirred under hydrogen pressure (~40 psi) for 24 hours. After completion of the reaction, the mixture was filtered through diatomaceous earth and the filtrate was evaporated. The crude product was purified by fast chromatography (eluent: dichloromethane:methanol:ammonia (880) 90:10:1) to afford tert-butyl (S)-2-(2-aminoethyl)pyrrolidine-1-carboxylate (1.18 g, 80% yield).1H NMR (CDCl3) δ: 3.90 (1H, m), 3.30 (2H, m), 2.71 (2H, t). 1.87-1.45 (17H, m).
References
[1] Patent: EP1056733, 2004, B1. Location in patent: Page 34-35
[2] Patent: WO2006/116764, 2006, A1. Location in patent: Page/Page column 121; 133-134
[3] Tetrahedron Letters, 1994, vol. 35, # 47, p. 8805 - 8808
[4] Patent: WO2004/58705, 2004, A2. Location in patent: Page 40-42
[5] Organic and Biomolecular Chemistry, 2010, vol. 8, # 16, p. 3742 - 3750
