反应详情

A stirred solution of 2-hydroxybenzenecarbothioamide 3a (5.36 g, 35.0 mmol), ethyl 4-chloroacetoacetate (6.34 g, 38.5 mmol) in dry THF (70 mL) was heated to reflux under nitrogen for 2.5 days. At ambient temperature, the mixture was diluted with EtOAc (200 mL), then cautiously treated with saturated aq. NaHCO3 (40 mL), and followed by adding solid NaHCO3 in small portions until CO2 evolution ceased. The organic layer was separated, washed with brine (40 mL×2), dried over MgSO4, and filtered. After concentration in vacuo, the oily residue was chromatographed on silica gel gradient EtOAc/CH2Cl2 :0-4%) to provide 4a (8.53 g, 93%) as a white solid, which was recrystallized from toluene/hexane at -30° C. mp 35.5-36.5° C.; IR (neat) 3120, 1740, 480, 1225 cm-1 ; 1H NMR (DMSO-d6) δ1.15 (3H, t, J=7.1 Hz, CH3), 3.84 (2H, t, CH2), 4.07 (2H, q, J=7.1 Hz, CH2), 6.89 (1H, S, J=7.8 Hz, Ar), 6.97 (1H, d, J=7.8 Hz, Ar), 7.26 (1H, t, J=7.8 Hz, Ar), 7.48 (1H, s, 7.93 (1H, d, J=7.8 Hz, Ar, 11.29 (1H, s, OH); FABMS m/z 263 (M30 ), 264 (M+ +1); Anal. Calcd for C13H13NO3S: C, 59.30; H, 4.98; N, 5.32. Found: C, 59.16; H, 4.97; N, 5.50.

1. temperatureto reflux under nitrogen for 2.5 days
2. customThe organic layer was separated
3. washwashed with brine (40 mL×2)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationAfter concentration in vacuo
7. customthe oily residue was chromatographed on silica gel gradient EtOAc/CH2Cl2