Reaction #2200598

Reaction equation

methylboronic acid

cesium fluoride

1,4-bis(diphenylphosphino)butane

methyl 4-amino-3,6-dichloro-5-fluoropyridine-2-carboxylate

→

methyl 4-amino-3-chloro-5-fluoro-6-methylpyridine-2-carboxylate

Solvents

acetonitrile

triethylamine

water

Conditions

Workup

1. 1
   Temperaturethe reaction mixture heated
2. 2
   Temperatureunder reflux overnight
3. 3
   TemperatureAfter cooling
4. 4
   Extractionthe mixture extracted with ethyl acetate
5. 5
   WashThe organic layer was washed with brine
6. 6
   Dryingdried (MgSO4)
7. 7
   Concentrationconcentrated
8. 8
   OtherThe residue was purified by column chromatography (33% ethyl acetate in hexane)

Procedure

A solution of methylboronic acid (0.17 g, 2.93 mmol), cesium fluoride (0.95 g, 6.27 mmol), 1,4-bis(diphenylphosphino)butane (0.09 g, 0.21 mmol), methyl 4-amino-3,6-dichloro-5-fluoropyridine-2-carboxylate (0.50 g, 2.09 mmol) and triethylamine (1 mL) in acetonitrile (20 mL) was purged for 15 minutes with nitrogen. Palladium acetate (0.05 g, 0.21 mmol) was then added and the reaction mixture heated under reflux overnight. After cooling, water was added and the mixture extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4), and concentrated. The residue was purified by column chromatography (33% ethyl acetate in hexane) to give methyl 4-amino-3-chloro-5-fluoro-6-methylpyridine-2-carboxylate (0.23 g, 1.05 mmol), mp 113-114° C.

Source