反应详情

To the crude 1-(3-(3-carbamoyl-5,6-dichloropyridin-2-yloxy)propyl)cyclopropyl 2,2,2-trifluoroacetate in MeCN (20 mL) was added POCl3 (700 mg, 4.6 mmol) and pyridine (720 mg, 9 mmol) at room temperature. After being stirred for 2 h at room temperature, the mixture was diluted with 30 mL of sodium hydroxide solution, then extracted with ethyl acetate (2×50 mL), the combined organic layers were washed with brine twice, dried over Na2SO4, concentrated and purified by column chromatography (silica gel, Petroleum ether:EtOAc=1:0 to 10:1) to give the product 1-(3-(5,6-dichloro-3-cyanopyridin-2-yloxy)propyl)cyclopropyl 2,2,2-trifluoroacetate (0.87 g, 97%). 1H-NMR (400 MHz, DMSO-d6) δ (ppm) 8.68 (s, 1H), 4.39 (t, 2H, J=6.4 Hz), 1.90 (m, 4H), 1.05 (t, 2H, J=6.8 Hz), 0.84 (t, 2H, J=6.8 Hz).

1. extractionextracted with ethyl acetate (2×50 mL)
2. washthe combined organic layers were washed with brine twice
3. dry with materialdried over Na2SO4
4. concentrationconcentrated
5. custompurified by column chromatography (silica gel, Petroleum ether:EtOAc=1:0 to 10:1)