反应详情

A solution of N-(N-tert-butyloxycarbonyl-aminomethyl)-N-(N1-thyminylacetyl)-β-alanine ethylester (5.45 g, 13.2 mmol) in THF (80 mL) and aqueous LiOH (0.5 M, 80 mL) was stirred at room temperature for 1 hour and extracted with ethyl acetate. The aqueous layer was acidified to pH 3.5 by dropwise addition of hydrochloric acid (4 M) and kept at 4° C. for 3 hours. The colorless precipitate was filtered, rinsed with water and dried in vacuo to give 4.40 g of the title compound, mp 196° C. (dec.). The filtrate was extracted with ethyl acetate, the organic phase dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was crystallized from MeOH/ethyl acetate/hexane to give 280 mg additional title compound for an overall yield of 92%. TLC (CHCl3/MeOH/NEt3 7:2:1, UV-detection): Rf(N-(N-tert-butyloxycarbonyl-aminomethyl)-N-(N1-thyminylacetyl)-β-alanine ethylester)=0.94, Rf(the title compound)=0.52). 1H NMR (DMSO-d6) (two rotamers, ratio 3:1) δ1.46, 1.50* (2s, 9H, t-Bu), 1.83 (s, 3H, T-CH3), 2.52*, 2.73 (2t, J=7.5 Hz, 2H, NCH2CH2), 3.54*, 3.64 (2t, J=7.3 Hz, 2H, NCH2CH2), 4.64, 4.69 (2d, J=6.4 Hz, J=7.0 Hz. 13C NMR (major rotamer) (DMSO-d6) δ11.9 (T, CH3), 28.1 (t-Bu-CH3), 32.2 (CH2CO), 41.6 (NCH2CH2), 48.1 (T(N1)CH2), 53.2 (NCH2N), 60.0 (OCH2), 78.9 (C(CH3)3) 108.2 (T, CCH3), 142.0 (CH), 151.1(T, NC(O)N), 155.7 (carbamate C═O), 164.4 (T, C═O), 166.9 (tert. amide C═O), 172.7 (carboxylic acid C═O) ppm. FAB-MS: m/z=385.15 (M+H)+. Anal. Calcd. for C16H24N4O7 (384.39): C, 50.00; H, 6.29; N, 14.58. found C, 49.95, H, 6.40; N, 14.23.

1. extractionextracted with ethyl acetate
2. additionThe aqueous layer was acidified to pH 3.5 by dropwise addition of hydrochloric acid (4 M)
3. filtrationThe colorless precipitate was filtered
4. washrinsed with water
5. customdried in vacuo