Synthesis
General procedure for the synthesis of 2-methoxy-1-pyrrolidine from 2-pyrrolidone and dimethyl sulfate: 23 mL (1 equiv.) of dimethyl sulfate was added slowly and dropwise to a solution of 20.03 g (0.235 mol) of 2-pyrrolidone dissolved in 85 mL of benzene, after which the reaction mixture was heated to 70 °C and kept at reflux for 3 hours. Upon completion of the reaction, the mixture was cooled to room temperature and then 19 mL of 15 N sodium hydroxide solution was added. The reaction mixture was transferred to a partition funnel and the aqueous phase was extracted three times with benzene. The organic phases were combined and dried over anhydrous sodium sulfate, followed by evaporation of the solvent under reduced pressure. The residue was purified by vacuum distillation to afford 2-methoxy-1-pyrrolidine as a colorless liquid in 58% yield. The boiling point of the product was 37 °C (10^-2 mbar).1H NMR (CDCl3, 100 MHz) data were as follows: δ 1.97 (m, 2H), 2.41 (t, 2H), 3.61 (t, 2H), 3.75 (s, 3H).
References
[1] Arkivoc, 2016, vol. 2016, # 5, p. 118 - 141
[2] Journal of Organic Chemistry, 1995, vol. 60, # 9, p. 2912 - 2915
[3] Organic Preparations and Procedures International, 1992, vol. 24, # 2, p. 147 - 158
[4] Journal of Medicinal Chemistry, 2001, vol. 44, # 10, p. 1588 - 1593
[5] Journal of Medicinal Chemistry, 2007, vol. 50, # 25, p. 6307 - 6315
