Reacción #1924635

Ecuación de reacción

3,4-dimethylphenylboronic acid

cesium fluoride

1,4-bis(diphenylphosphino)butane

methyl 4-amino-3,6-dichloropyridine-2-carboxylate

→

methyl 4-amino-3-chloro-6-(3,4-dimethylphenyl)pyridine-2-carboxylate

Rendimiento 50.0%

Disolventes

acetonitrile

triethylamine

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe reaction mixture heated
2. 2
   Temperaturaunder reflux for three hours
3. 3
   workup.ADDITIONwas added
4. 4
   Extracciónthe mixture extracted with ethyl acetate (2×100 mL)
5. 5
   LavadoThe organic layer was washed with brine (100 mL)
6. 6
   Secadodried (NaSO4)
7. 7
   Concentraciónconcentrated
8. 8
   OtroThe residue was purified by column chromatography (33 percent ethyl acetate in hexane)

Procedimiento

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.

Fuente