反应详情

温度

95 °C

To a suspension of 2-(2-fluoro-4-iodophenylamino)-6-formylaminomethylnicotinic acid methyl ester (11.6 g, 27.4 mmol) in toluene (160 mL) was added phosphorous (V) oxychloride (5.1 mL, 54.8 mmol) and the reaction mixture heated at 95° C. for 1 hour. The reaction mixture was concentrated in vacuo and the resultant residue poured onto ice. The mixture was washed with aqueous saturated sodium hydrogen carbonate solution (40 mL) and the aqueous layer extracted twice with ethyl acetate (2×30 mL). The combined organic extracts were washed with brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-70% ethyl acetate in DCM) to yield the title compound as a brown oil (5.6 g, 50%). LCMS (Method B): RT=3.62 min, M+H+=412.

1. concentrationThe reaction mixture was concentrated in vacuo
2. additionthe resultant residue poured onto ice
3. washThe mixture was washed with aqueous saturated sodium hydrogen carbonate solution (40 mL)
4. extractionthe aqueous layer extracted twice with ethyl acetate (2×30 mL)
5. washThe combined organic extracts were washed with brine (30 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo