The general procedure for the synthesis of methyl 1-Boc-2-pyrrolidinecarboxylate from Boc-L-proline and iodomethane was as follows: potassium carbonate (K2CO3, 1.1 kg, 8.0 mol) and iodomethane (CH3I, 659 g, 4.65 mol) were added to a 1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid (500 g, 2.32 mol) in a solution of dimethylformamide (DMF, 2.5 L). The reaction mixture was stirred at room temperature for 12 h followed by filtration. The filtrate was concentrated under vacuum. The residue was dissolved in ethyl acetate (EtOAc, 2 L), washed sequentially with water (2 x 1 L) and brine (1 L), dried with magnesium sulfate (MgSO4), and finally concentrated under vacuum to afford methyl 1-Boc-2-pyrrolidinecarboxylate (417.8 g, 96% yield) as a yellow oil.1H NMR (CDCl3) data were as follows: δ 1.37 (9H m), 1.72-1.84 (3H, m), 2.15 (1H, m), 3.26-3.51 (2H, m), 3.65 (3H, s), 4.17 (1H, m).
