反应详情

温度

75 °C

To a solution of tert-butyl (1R,3R,4S)-4-((benzyloxycarbonyl)amino)-3-carbamothioylcyclohexylcarbamate (0.5 g, 0.0012 mol) in dry benzene (20 mL) under nitrogen was added chloroacetone (0.34 g, 0.0036 mol) and the reaction mixture was heated at 75° C. over night. Benzene was removed under vacuum and the crude was extracted with ethyl acetate. The organic layer was washed with brine, concentrated and purified by recrystallisation from ether to give 0.24 g (44%) of tert-butyl (1R,3R,4S)-4-((benzyloxycarbonyl)amino)-3-(4-methylthiazol-2-yl)cyclohexylcarbamate as a white solid. 1H NMR (400 MHz, CDCl3) δ 1.44 (s, 9H), 1.65 (m, 3H), 1.78 (m, 2H), 2.19 (m, 2H), 2.42 (s, 3H), 3.49 (m, 1H), 3.70 (m, 1H), 4.05 (m, 1H), 5.04 (s, 2H), 5.29 (bs, 1H), 6.75 (s, 1H), 7.34 (m, 5H); 13H NMR (400 MHz, CDCl3) δ 16.4, 27.4, 27.8, 32.7, 41.9, 46.5, 49.7, 66.0, 78.5, 112.3, 127.3, 127.4, 127.8, 135.9, 151.8, 154.6, 155.2, 169.2. MS found: (M+H)+=446.

1. customBenzene was removed under vacuum
2. extractionthe crude was extracted with ethyl acetate
3. washThe organic layer was washed with brine
4. concentrationconcentrated
5. custompurified by recrystallisation from ether