Synthesis
Example A: Synthesis of N-benzyl-3-hydroxymethylpyrrolidine
Step a: Reduction of methyl 1-benzyl-5-oxopyrrolidine-3-carboxylate to 1-benzyl-3-hydroxymethylpyrrolidine
Under an inert atmosphere, methyl 1-benzyl-5-oxopyrrolidine-3-carboxylate (1.0 equiv, commercially available) was dissolved in toluene and the mixture was cooled to 0 °C. To the cooled mixture was slowly added a dimethyl sulfide solution of borane-dimethyl sulfide complex (3.75 equiv.). The reaction mixture was heated to 100°C-110°C and refluxed for 16 hours. Upon completion of the reaction, the mixture was cooled to room temperature, further cooled to -5 °C to -10 °C, and then sodium bicarbonate solution was added dropwise. The mixture was slowly warmed to room temperature and then refluxed for 2 hours. After the reaction mixture was cooled, the organic layer was separated and the aqueous layer was extracted with toluene. The combined toluene layers were washed sequentially with water and brine. Finally, the organic solvent was removed by evaporation under reduced pressure to afford the target product N-benzyl-3-hydroxymethylpyrrolidine in 99.14% yield.
References
[1] Patent: WO2006/18708, 2006, A2. Location in patent: Page/Page column 21-22
[2] Letters in Organic Chemistry, 2011, vol. 8, # 3, p. 155 - 162
[3] Patent: US2004/147502, 2004, A1. Location in patent: Page/Page column 36-37
[4] Organic Letters, 1999, vol. 1, # 5, p. 799 - 801
[5] Patent: US2005/165005, 2005, A1. Location in patent: Page/Page column 59-60
