反应详情

To a solution of N-(2-fluoro-4-iodo-phenyl)-2-pyrimidin-4-ylmethyl-malonamic acid ethyl ester (4 g, 9.02 mmol) in toluene (120 mL) was added phosphorous (V) oxychloride (4.2 mL, 45.1 mmol). The reaction was heated at reflux for 16 hours then concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (30 mL), washed with saturated aqueous sodium bicarbonate solution (20 mL) and the aqueous fraction extracted twice with ethyl acetate (2×10 mL). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-40% ethyl acetate in cyclohexane) to yield a dark brown solid. The solid was triturated with ether (10 mL) to yield the title compound as a light brown solid (0.63 g, 16%). LCMS (Method B): RT=3.95 min, M+H+=426.

1. temperatureThe reaction was heated
2. temperatureat reflux for 16 hours
3. concentrationthen concentrated in vacuo
4. dissolutionThe resultant residue was dissolved in ethyl acetate (30 mL)
5. washwashed with saturated aqueous sodium bicarbonate solution (20 mL)
6. extractionthe aqueous fraction extracted twice with ethyl acetate (2×10 mL)
7. washThe combined organic fractions were washed with brine
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo
10. customto yield a dark brown solid
11. customThe solid was triturated with ether (10 mL)