反应详情

A solution of 3,4-dimethylphenylboronic acid (2.1 g, 14.0 mmol), cesium fluoride (6.3 g, 41.5 mmol), 1,4-bis(diphenylphosphino)butane (0.5 g, 1.2 mmol), methyl 4-amino-3,6-dichloropyridine-2-carboxylate (2.5 g, 10.0 mmol) and triethylamine (5 mL) in acetonitrile (100 mL) was sparged for thirty minutes with nitrogen. Palladium acetate (0.3 g, 1.2 mmol) was added and the reaction mixture heated under reflux for three hours. After cooling water (200 mL) was added and the mixture extracted with ethyl acetate (2×100 mL). The organic layer was washed with brine (100 mL), dried (NaSO4), and concentrated. The residue was purified by column chromatography (33 percent ethyl acetate in hexane) to give methyl 4-amino-3-chloro-6-(3,4-dimethylphenyl)pyridine-2-carboxylate (1.4 g, 5.0 mmol), mp 154-156° C.

1. temperaturethe reaction mixture heated
2. temperatureunder reflux for three hours
3. additionwas added
4. extractionthe mixture extracted with ethyl acetate (2×100 mL)
5. washThe organic layer was washed with brine (100 mL)
6. dry with materialdried (NaSO4)
7. concentrationconcentrated
8. customThe residue was purified by column chromatography (33 percent ethyl acetate in hexane)