反应详情

温度

110 °C

A suspension of isopropyl 4-(5-cyano-4-(methylthio)-6-oxo-1,6-dihydropyridin-2-yl)benzoate (1.6 g, 4.87 mmol) in phosphoryl trichloride (14.94 g, 97 mmol) was heated to 110° C. for 60 h, cooled to room temperature and carefully added to cold water (50 mL). The resultant mixture was carefully quenched with saturated. NaHCO3(200 mL), and extracted with ethyl acetate (3×200 mL). The combined organic extracts were washed with brine (100 mL), dried (MgSO4) and concentrated to give a mixture of acid and ester. The material was treated with DMF (10 ml) and 6 N HCl (10 ml), heated to 100° C. for 1 h, cooled to room temperature and diluted with water (50 ml) and filtered. The solid was washed with water (10 ml), dried under vacuum to give 4-(6-chloro-5-cyano-4-(methylthio)pyridin-2-yl)benzoic acid (1.45 g. 70% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.31 (2H, d, J=8.53 Hz), 8.10 (2H, d, J=8.53 Hz), 7.95 (1H, s), 2.87 (3H, s); MS (ES+) m/z: 305 (M+H); LC retention time: 3.45 min (analytical HPLC Method A).

1. temperaturecooled to room temperature
2. customThe resultant mixture was carefully quenched with saturated
3. extractionNaHCO3(200 mL), and extracted with ethyl acetate (3×200 mL)
4. washThe combined organic extracts were washed with brine (100 mL)
5. dry with materialdried (MgSO4)
6. concentrationconcentrated
7. customto give
8. temperatureheated to 100° C. for 1 h
9. temperaturecooled to room temperature
10. filtrationfiltered
11. washThe solid was washed with water (10 ml)
12. customdried under vacuum