Reacción #2336578

Ecuación de reacción

4-amino-3,6-dichloropyridine-2-carboxylic acid, methyl ester

2-fluoro-3-methoxy-4-methylphenyl boronic acid

cesium fluoride

→

4-amino-3-chloro-6-(2-fluoro-3-methoxy-4-methylphenyl)pyridine-2-carboxylic acid, methyl ester

Rendimiento 18.2%

Disolventes

dimethoxyethane

water

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Extracciónextracted with ethyl acetate (2×15 mL)
2. 2
   LavadoThe combined extracts were washed with brine
3. 3
   Secadodried (sodium sulfate)
4. 4
   Concentraciónconcentrated
5. 5
   OtroThe residue was purified by chromatography (33% ethyl acetate in hexanes)

Procedimiento

A solution of 4-amino-3,6-dichloropyridine-2-carboxylic acid, methyl ester (0.24 g, 1.1 mmol), 2-fluoro-3-methoxy-4-methylphenyl boronic acid (0.30 g, 1.63 mmol) and cesium fluoride (3.0 g, 3.26 mmole) in dimethoxyethane (2 mL) and water (2 mL) was purged with a stream of nitrogen for 15 minutes before adding dichlorobis(triphenylphosphine) palladium (0.07 g, 0.1 mmol) and then heated to 85° C. for 2 hours. The reaction mixture was diluted with water (15 mL) and extracted with ethyl acetate (2×15 mL). The combined extracts were washed with brine, dried (sodium sulfate) and concentrated. The residue was purified by chromatography (33% ethyl acetate in hexanes) to give 4-amino-3-chloro-6-(2-fluoro-3-methoxy-4-methylphenyl)pyridine-2-carboxylic acid, methyl ester (0.08 g, 0.2 mmol): mp 95-96° C.

Fuente