[Synthesis]
Dimethyldichlorosilane (148.4 g, 1.15 mol) was slowly added dropwise to an anhydrous pyridine (500 ml) suspension of L-proline (115.1 g, 1.00 mol) at 0 °C and under argon protection. The reaction mixture was stirred at 0 °C for 2 h. After that, dry ethylamine (180.3 g, 4.00 mol) was added at the same temperature. Subsequently, the reaction mixture was transferred to room temperature and continued stirring for 1 hour. The precipitate was separated from the solution by filtration and the solvent was removed under reduced pressure. The resulting viscous residue was dissolved in 5% sodium carbonate solution (300 ml) and the aqueous layer was subsequently washed with ether-hexane (1:1, 400 ml). The aqueous phase was concentrated under reduced pressure and 17% hydrochloric acid (200 ml) was added to the crude product, L-proline acetamide, and again evaporated under reduced pressure. Methanol (400 ml) was added to the residue and the solvent was removed under reduced pressure after filtration to remove inorganic salts. After addition of ether (500 ml) and stirring for 1 hr, pure (S)-N-ethylpyrrolidine-2-carboxamide hydrochloride was isolated from the solution by filtration. The yield was 148.4 g (83.1% yield) as white crystals with a melting point of 98-100 °C (literature value 97 °C).HPLC purity 99.24%. Specific optical rotation [α]D27 -52.48 (c 0.3, water).IR spectrum (cm-1): 3509, 3453, 2971, 2927, 2593, 2471, 1686, 1577, 1471, 1396, 1290, 1259, 1147, 1055, 816, 565.1H NMR (δ, ppm, J/Hz ): 1.16 (3H, t, J=7.2, CH2CH3); 1.96-2.11 (3H, m, 3-CHA, 4-CH2); 2.50-2.64 (1H, m, 3-CHB); 3.19-3.35 (2H, m, 5-CH2); 3.43-3.52 (2H, m, CH2CH3); 4.62-4.71 (1H, m, 2-CH); 7.89 (1H, br.s, N+H); 10.46 (1H, br.s, N+H); 8.68 (1H, t, J=7.1, CONH).13C NMR (δ, ppm): 12.9; 23.3; 29.2; 34.3; 46.1; 59.4; 168.4.Mass spectra (m/z. Irel%): 143 [M-Cl]+ (100). Elemental analysis measured values (%): C 47.13; H 8.55; N 15.81. C7H15ClN2O calculated values (%): C 47.06; H 8.46; N 15.68. |