反应详情

温度

85 °C

To a stirred suspension of 4-chloro-3-ureido-benzoic acid (26 g, 121 mmol) in ethanol (375 mL) was added 1,1,1-trifluoro-2,4-pentanedione (28 g, 182 mmol) and concentrated (95%) sulfuric acid (50 mL). The reaction mixture was heated at 85° C. for 6 h. After cooling to room temperature, the mixture was partitioned between water (500 mL) and DCM (1 L) and to this was added 6N aq. NaOH, until pH 9-10 attained. The DCM layer was separated and dried over MgSO4 and filtered. Concentration in vacuo gave an orange oil which was purified via silica gel flash chromatography (eluting with a gradient of 10% to 25% EtOAc in hexanes). The resulting orange solid was further triturated with diethyl ether to give 4-chloro-3-(6-methyl-2-oxo-4-trifluoromethyl-2H-pyrimidin-1-yl)-benzoic acid ethyl ester (3.77 g, 9%) as a colorless solid. MS (M+H)+: 360.8, tR=2.670 min (method 1); 1H NMR (CDCl3) δ 8.16 (1H, dd, J=8.4, 2.1 Hz), 8.00 (1H, d, J=1.8 Hz), 7.70 (1H, d, J=8.4 Hz), 6.63 (1H, s), 4.39 (2H, q, J=6.9 Hz), 2.15 (3H, s), 1.39 (3H, t, J=6.9 Hz).

1. concentrationconcentrated (95%) sulfuric acid (50 mL)
2. temperatureAfter cooling to room temperature
3. customthe mixture was partitioned between water (500 mL) and DCM (1 L)
4. additionto this was added 6N aq. NaOH
5. customThe DCM layer was separated
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationConcentration in vacuo
9. customgave an orange oil which
10. customwas purified via silica gel flash chromatography (
11. washeluting with a gradient of 10% to 25% EtOAc in hexanes)
12. customThe resulting orange solid was further triturated with diethyl ether