H-PRO-NHET HCL

Me2SiCl2 (148.4 g, 1.15 mol) was added dropwise to a suspension of L-proline (1) (115.1 g, 1.00 mol) in dry pyridine (500 ml) at 0°C under argon atmosphere. The reaction mixture was stirred at 0°C for 2 h and then dry EtNH2 (180.3 g, 4.00 mol) was added at the same temperature. The reaction mixture was subsequently stirred at room temperature for 1 h. The residue precipitated during the process was separated from the solution by filtration, and the solvent was removed under low pressure. The viscous residue was then dissolved in 5percent Na2CO3 solution (300 ml), and the resulting solution was washed with Et2O–hexane (1:1, 400 ml). The water layer was concentrated under low pressure, 17percent HCl (200 ml) was added to the obtained residue of crude L-proline ethylamide, and the resulting mixture was evaporated again in vacuo. MeOH (400 ml) was added to the residue, after which the inorganic salts were filtered off and the solvent was removed under low pressure. After adding Et2O (500 ml) and stirring for 1 h, pure hydrochloride 2 was separated from the solution by filtration. Yield 148.4 g (83.1percent), white crystals, mp 98-100°C (mp 97°C [14]). Purity 99.24percent (HPLC). [α]D27 -52.48 (c 0.3, H2O). IR spectrum, ν, cm-1: 3509, 3453, 2971, 2927, 2593, 2471, 1686, 1577, 1471, 1396, 1290, 1259, 1147, 1055, 816, 565. 1H NMR spectrum, 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 spectrum, δ, ppm: 12.9; 23.3; 29.2; 34.3; 46.1; 59.4; 168.4. Mass spectrum, m/z (Irel, percent): 143 [M–Cl]+ (100). Found, percent: C 47.13; H 8.55; N 15.81. C7H15ClN2O. Calculated, percent: C 47.06; H 8.46; N 15.68.