1Department of Pharmaceutical Analysis, 2Department of Medicinal Chemistry, University of Szeged, Dóm tér 8., H-6720 Szeged, Hungary. *Phone: +36 62 54 51 45, Fax: +36 62 42 52 62, E-mail: [email protected]
Received: 10 April 2000 / Accepted: 25 April 2000 / Published: 10 July 2000
The synthesis of N-Fmoc-L-serine amide was performed by the well known Schotten-Baumann acylation method [1]. L-Serine amide hydrochloride (1.00 g, 7.1 mmol) and 1.50 g (14.2 mmol) of Na2CO3 were dissolved in dioxane-water 2:1 (45 ml). Then a solution of 2.00 g (7.7 mmol, 1.1 equivalent) of Fmoc chloride in dioxane (20 ml) was added dropwise over 1 h. The reaction mixture was stirred overnight at room temperature. According to TLC analysis, all the starting material was converted. The reaction mixture was evaporated, the resulting solid was triturated with 10% aq. NaHSO4 (50 ml), filtered, washed with H2O and ether and dried. As the crude product does not dissolve in apolar solvents nor ethyl acetate, crystallization was performed in tetrahydrofuran-ethyl acetate (1:3 v/v) to give 1.87 g (81%) of the title compound as a white solid.
Mp.: 155-156 °C.
[a]D20= +13.7 (c 2.5, tetrahydrofuran).
1H NMR (DMSO-d6, 500 MHz): 3.56 (m, 2H, CH2OH); 3.96 (m, 1H, CHNH); 4.21 (t, J 6.6 Hz, 1H, CHCH2O); 4.26 (d, J 6.2 Hz, 2H, CH2O); 4.82 (t, J 5.7 Hz, 1H, OH); 7.04 (s, 1H, 1/2 NH2); 7.26 (s, 1H, 1/2 NH2); 7.13 (d, J 8.3 Hz, 1H, NH); 7.32 (dd, J 7.4 Hz, 2H, aromatic CH), 7.40 (dd, J 7.4 Hz, 2H, aromatic CH), 7.72 (d, J 5.2 Hz, 2H, aromatic CH), 7.87 (d, J7.5 Hz, 2H, aromatic CH).
13C NMR (DMSO-d6, 125 MHz, assignment based on J-modulated spin-echo, HMQC and COSY experiments): 46.6 (CHCH2); 57.0 (CHNH); 61.7 (CH2OH); 65.6 (CH2O); 120.0; 125.2; 127.0; 127.6 (aromatic CHs); 140.6; 143.8 (aromatic Cqs); 155.8 (CONH); 172.0 (CONH2).
ESI-MS (in methanol-H2O, m/z, %): 326.9 (64, [M+H]+), 343.9 (61, [M+NH4]+), 348.9 (100, [M+Na]+), 653.3 (3, [2M+H]+), 675.3 (13, [2M+Na]+).
Anal calcd. for C18H18N2O4 (326.35): C, 66.25; H,5.56; N, 8.58; found C, 66.11; H, 5.45; N, 8.55 %.
Reference
1. Kocienski, P. Protecting Groups; Georg Thieme Verlag: Stuttgart, 1994: p 204.
Sample availability: available from the authors and MDPI (MDPI ID 18866).
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