Synthesis
Step B: (i) Synthesis of (R)-2-methylpyrrolidine hydrochloride; (i) (R)-tert-butyl 2-methylpyrrolidine-1-carboxylate (22.7 g, 123 mmol) was dissolved in a dioxane solution (100 mL) of 4 M hydrogen chloride and the reaction was stirred for 30 min at room temperature. The reaction was monitored by TLC (unfolding agent ratio 2:1 ethyl acetate/hexane) to confirm complete consumption of the raw material. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. The crude product was dissolved in a solvent mixture of acetonitrile and toluene and the solvent was again removed by distillation under reduced pressure. The resulting white solid was dried overnight under reduced pressure to give the title compound (14.6 g) in 98% yield.1H NMR (400 MHz, CDCl3) δ 1.55 (d, J=6.57 Hz, 3H), 1.66-1.77 (m, 1H), 1.95-2.04 (m, 1H), 2.05-2.23 (m, 2H). 3.25-3.36 (m, 1H), 3.37-3.48 (m, 1H), 3.62-3.74 (m, 1H), 9.38 (s, 1H), 9.86 (s, 1H).
References
[1] Patent: WO2008/5338, 2008, A1. Location in patent: Page/Page column 80
[2] Tetrahedron, 2006, vol. 62, # 18, p. 4584 - 4589
[3] Patent: US2004/260100, 2004, A1. Location in patent: Page 8
[4] Patent: WO2006/19833, 2006, A1. Location in patent: Page/Page column 44
[5] Organic and Biomolecular Chemistry, 2010, vol. 8, # 20, p. 4533 - 4535
