A trifluoroacetic acid solution of 44.0 g (0.4 mol) at a mass concentration of 10% was prepared by adding 1530.0 g (6.5 mol) of N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine, 31.80 g (3.7 mol) of methyl acrylate, and 38 mL of dichloromethane to a 250 mL multi-neck reaction flask. The trifluoroacetic acid solution was added slowly dropwise at 0 °C, and after completion of the dropwise addition, the reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, the mixture was concentrated under reduced pressure and the residue was washed sequentially with saturated sodium bicarbonate solution and saturated sodium chloride solution. The organic phases were combined, dried with anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give 1420.0 g of 1-benzylpyrrolidine-3-carboxylic acid methyl ester crude product in 100% yield.
[1] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 19, p. 4861 - 4866
[2] Organic Process Research and Development, 2009, vol. 13, # 2, p. 292 - 296
[3] Synthesis, 2006, # 16, p. 2646 - 2648
[4] Synlett, 2015, vol. 26, # 13, p. 1815 - 1818
[5] Chemical & Pharmaceutical Bulletin, 1985, vol. 33, # 7, p. 2762 - 2766
