[Synthesis]
L-proline (5.00 g, 43.44 mmol, 1.0 eq.) and potassium hydroxide (9.78 g, 174.3 mmol, 4 eq.) were dissolved in isopropanol (50 mL) and stirred at 40 °C until the solution was clarified. Subsequently, benzyl chloride (8.25 g, 7.50 mL, 65.2 mmol, 1.5 eq.) was added and the reaction continued to be stirred at 40 °C for 6 hours. Upon completion of the reaction, the reaction solution was neutralized with concentrated aqueous hydrochloric acid to pH 5-6. After neutralization, chloroform (30 mL) was added and the mixture was stirred overnight. The resulting precipitate was removed by filtration and the precipitate was washed with chloroform (30 mL). The organic phases were combined and the solvent was evaporated under vacuum. The resulting residue was treated with acetone (30 mL) to precipitate the crude product, which was filtered and washed with acetone to afford the white solid product (S)-1-benzylpyrrolidine-2-carboxylic acid (5.39 g, 26.26 mmol, 60% yield). The product was characterized as follows: Rf 0.09 (dichloromethane:methanol = 9:1); melting point 175 °C (literature value 167 °C); νmax(neat)/ cm-1 3041, 2992, 2969, 1634, 1450, 1375, 1311, 1190, 753, 704; 1H NMR (300 MHz, D2O) δ 7.53 (s, br, 5H, Ar-H), 4.40 (s, 2H, CH2Ph), 4.01 (dd, 1H, J = 6.7, 9.3 Hz, CHCO2H), 3.73-3.58 (m, 1H, CH2CH2aN), 3.38-3.21 (m, 1H, CH2CH2bN), 2.62-2.41 (m, 1H, CH2aCH), 2.27-1.89 (m, 3H, CH2bCH and CH2CH2N); 13C NMR (75 MHz, D2O) δ 173.54, 130.55, 130.05, 129.96, 129.25, 68.24, 58.30, 54.61, 28.79, 22.78; HRMS m/z ( ESI) 206.1215 ([M + H]+, calculated value 206.1165). |
[References]
[1] Organic and biomolecular chemistry, 2003, vol. 1, # 17, p. 3010 - 3014
[2] Tetrahedron Asymmetry, 1998, vol. 9, # 23, p. 4249 - 4252
[3] Advanced Synthesis and Catalysis, 2014, vol. 356, # 10, p. 2203 - 2208
[4] Journal of Organic Chemistry, 2003, vol. 68, # 18, p. 7104 - 7107
[5] Journal of Organic Chemistry, 2011, vol. 76, # 6, p. 1513 - 1520 |