(3R)-(-)-1-Benzyl-3-(methylamino)pyrrolidine

131878-23-4

144043-17-4

The general procedure for the synthesis of (R)-1-benzyl-3-methylaminopyrrolidine from (R)-1-benzyl-3-(tert-butoxycarbonylamino)pyrrolidine was as follows: tert-butyl (R)-(1-benzylpyrrolidin-3-yl)carbamate (3.20 g, 11.6 mmol) was dissolved in 58.0 mL of tetrahydrofuran in a 100 mL round-bottom flask. The system was cooled to -40°C and lithium aluminum hydride (2.64 g, 69.6 mmol) was added slowly. The reaction mixture was refluxed for 4 hours and then cooled again to -40°C. The reaction was quenched by the addition of 2.70 mL of deionized water, 2.70 mL of 15% sodium hydroxide solution, and 8.10 mL of deionized water. Celite 545 was then added, stirred for 30 minutes and filtered through a pad of Celite 545. The filtrate was concentrated under reduced pressure and the residue was extracted three times with methylene chloride. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by fast column chromatography (methanol:methylene chloride:ammonium hydroxide = 5:90:5). After removal of the solvent in vacuo, 2.17 g (R)-1-benzyl-N-methylpyrrolidin-3-amine was obtained (98.6% yield).1H NMR (400 MHz, CDCl3) δ 7.34-7.24 (m, 5H), 3.62 (s, 2H), 3.25-3.19 (m, 1H), 2.74 (dd, J = 9.4, 6.8 Hz, 1H ), 2.64 (dt, J = 8.6, 6.0 Hz, 1H), 2.52 (dt, J = 8.4, 6.0 Hz, 1H), 2.41-2.37 (m, 1H), 2.38 (s, 3H), 2.19-2.09 (m, 1H), 2.02 (bs, 1H), 1.63-1.56 (m, 1H).