反应详情

Potassium phosphate tribasic (13.84 g, 65.2 mmol), palladium acetate (0.390 g, 1.739 mmol), methyl 2-bromo-6-methylisonicotinate (5 g, 21.73 mmol), 5-chloro-2-fluorophenylboronic acid (5.68 g, 32.6 mmol) and dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (1.521 g, 3.26 mmol) were combined in toluene (70 mL) and water (14 mL) and heated at 110° C. in an oil bath for 1 hour. The reaction was then cooled and diluted with water (30 mL), filtered through Celite® and the layers were separated. The aqueous layer was extracted with ether and the combined organic layers were dried over sodium sulfate, filtered, and concentrated to give a residue. The residue was dissolved in ethyl acetate/dichloromethane and absorbed onto silica gel before chromatography on silica eluting with 10% ethyl acetate in hexanes to give an off white powder which was dissolved in dichloromethane, dried onto silica gel and further purified by chromatography on silica using a step gradient (0-10% ethyl acetate/hexanes) to give methyl 2-(5-chloro-2-fluorophenyl)-6-methylisonicotinate (1.86 g, 30.6% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.64-2.68 (3H, m) 3.91-3.95 (3H, m) 7.45 (1H, dd, J=11.12, 8.84 Hz) 7.59 (1H, ddd, J=8.84, 4.29, 2.78 Hz) 7.75-7.81 (1H, m) 8.01 (1H, dd, J=6.57, 2.78 Hz) 8.06 (1H, s). ESI-MS: m/z 280.1 (M+H).

1. temperatureThe reaction was then cooled
2. filtrationfiltered through Celite®
3. customthe layers were separated
4. extractionThe aqueous layer was extracted with ether
5. dry with materialthe combined organic layers were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customto give a residue
9. customabsorbed onto silica gel before chromatography on silica eluting with 10% ethyl acetate in hexanes
10. customto give an off white powder which
11. customdried onto silica gel
12. customfurther purified by chromatography on silica using a step gradient (0-10% ethyl acetate/hexanes)