General procedure for the synthesis of N-benzyl-D-proline from benzyl chloride and D-proline: a suspension of D-proline (115 g, 1 mol), potassium hydroxide (168.3 g, 3 mol) and isopropanol (1 L) was stirred at 40°C until the suspension became clear. Subsequently, benzyl chloride (137.3 g, 1.1 mol) was slowly added and stirring was continued at 40°C for 6 hours. Upon completion of the reaction, the reaction mixture was cooled to 0-5°C and the pH was adjusted to 5-6 with concentrated hydrochloric acid (145 mL). the reaction mixture was diluted with chloroform (3 L) and stirred for 18 h. The reaction was purified by filtration. The resulting KCl was removed by filtration, the filtrate was concentrated and the crude product was recrystallized from acetone to give N-benzyl-D-proline in 79% yield (161.8 g). [39] The product was characterized as follows: 1H-NMR (CDCl3, ppm): δ 7.2-7.4 (m, 5H), 4.0-4.4 (dd, 2H), 3.8 (dd, 1H), 3.6-3.7 (m, 1H), 2.8 (dd, 1H), 1.8-2.4 (m, 4H). [40] Specific optical rotation [α]D25 = +28.4 (c = 1, EtOH). [41] Melting point 174-175°C.
