Step 1: Benzyl-trimethylsilylmethylamine (100 g, 517 mmol, 1 eq.) was loaded into a 1 L jacketed reactor, followed by 400 mL of THF. The reaction temperature was set to 15 C and 37% aqueous formaldehyde (53 mL, 647 mmol, 1.25 eq.) was added dropwise over ~10 min, keeping the temperature <30 C.
Step 2: In a separate reactor, 400 mL of THF (Tj=25°C) was charged, followed by the addition of N-methylmorpholine (2.85 mL, 26 mmol, 0.05 eq.), trifluoroacetic acid (TFA) (1 mL, 13 mmol, 0.025) eq.) and methyl acrylate (56.5 mL, 621 mmol, 1.2 eq. ). The solution was heated to 50-55 C and the solution from Reactor A was added dropwise over about 50 min. About 30 min after the end of the addition (completion of the reaction was judged by IPC), the reactor was cooled to room temperature and the solution was concentrated to about 500 mL. 250 mL of heptane was added, the organic phase was washed twice with 250 mL of water, the organic phase was dried over MgSO4, and the reaction was concentrated under reduced pressure (as low as 10-20 mbar, 45 C) to give 108 g of the crude product, N-Bn-pyrrolidine (90% yield) .
Step 3: 1 kg of N-Bn-pyrrolidine (4414 mmol, 1 eq.) was dissolved in 10 L of methanol and hydrogenated over 101 g of Pd/C (95 mmol Pd, 0.02 eq.) at atmospheric pressure. Upon completion of the reaction, the catalyst was filtered and the solution was concentrated to about 10 L. Methyl 3-pyrrolidinecarboxylate was obtained by adding 2 L of methanol and distilling at a constant volume.