反应详情

温度

-78 °C

N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-formamide (34 g, 0.14 mol) and triethylamine (34 g, 0.34 mol) are dissolved in dichloromethane (120 ml). Bis(trichloromethyl)carbonate (triphosgene, 16 g, 55 mmol) in dichloromethane (80 ml) is added at +5° C. The mixture is stirred for 4 hours at +5° C. and then cooled to −78° C. A solution of titanium tetrachloride (28 g, 0.15 mol) in dichloromethane (150 ml) is added and the mixture is stirred for 2 hours at −40° C. 4-Chlorobenzaldehyde (20 g, 0.14 mol) in dichloromethane (70 ml) is added dropwise and the mixture is stirred for 17 h at room temperature. The mixture is hydrolyzed with 5N HCl (80 ml), stirred 30 minutes at room temperature and washed with water. After evaporation of the organic layer the residue is submitted to flash-chromatography (ethyl acetate/hexane) to give 2-(4-chloro-phenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-acetamide. 1H-NMR (300 MHz, CDCl3): 2.54 (t, 1H, C≡CH), 2.72 (t, 2H, CH2CH2), 3.53 (t, 2H, CH2CH2), 3.84 (s, 3H, OCH3), 4.78 (m, 2H, OCH2), 4.98 (s, 1H, CHOH), 6.07 (bs, 1H, NH), 6.53-7.38 (m, 7H, CH arom.).

1. stirringthe mixture is stirred for 2 hours at −40° C
2. stirringthe mixture is stirred for 17 h at room temperature
3. stirringstirred 30 minutes at room temperature
4. washwashed with water
5. customAfter evaporation of the organic layer the residue