Reacción #44209

Ecuación de reacción

2-Fluoro-4-methylphenylamine

rac-2,2-bis(diphenylphosphino)-1,1′-binaphthyl

cesium carbonate

4-chloro-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester

→

desired product

Rendimiento 71.0%

4-(2-fluoro-4-methylphenylamino)-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester

Rendimiento 71.0%

Disolventes

EtOAc

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.WAITAfter 24 hours
2. 2
   Temperaturathe reaction mixture was cooled to room temperature
3. 3
   FiltraciónThe resulting precipitate was filtered
4. 4
   Lavadowashed with EtOAc
5. 5
   workup.ADDITIONThe filtrate was diluted with EtOAc
6. 6
   Lavadowashed with water
7. 7
   LavadoThe combined organic layers were washed with brine
8. 8
   Secadodried (Na2SO4)
9. 9
   Concentraciónconcentrated
10. 10
    OtroPurification by flash column chromatography (20:1 methylene chloride/MeOH)

Procedimiento

2-Fluoro-4-methylphenylamine (0.259 g, 2.07 mmol), palladium (II) acetate (0.046 g, 0.205 mmol), rac-2,2-bis(diphenylphosphino)-1,1′-binaphthyl (0.192 g, 0.308 mmol), and cesium carbonate (1.00 g, 3.08 mmol) were added to a solution of 4-chloro-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester (0.50 g, 2.05 mmol) in toluene (7 mL) in a sealed vial. After stirring 10 minutes, the mixture was heated to 80° C. After 24 hours, the reaction mixture was cooled to room temperature and diluted with EtOAc. The resulting precipitate was filtered and washed with EtOAc. The filtrate was diluted with EtOAc and washed with water. The aqueous layer was reextracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated. Purification by flash column chromatography (20:1 methylene chloride/MeOH) gave 0.048 g (71%) desired product.

Fuente