Reacción #44259

Ecuación de reacción

Methyl 2-chloro-5-fluoro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate

2-fluoro-4-(methylthio)aniline

lithium bis(trimethylsilyl)amide

→

desired product

Rendimiento 77.0%

methyl 5-fluoro-2-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate

Rendimiento 77.0%

Disolventes

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONafter the addition
2. 2
   workup.STIRRINGthe reaction mixture was stirred for 30 minutes at −78° C
3. 3
   OtroThe reaction was quenched by the addition of 1 M HCl until the pH of the reaction mixture
4. 4
   workup.ADDITIONdiluted with EtOAc and saturated NaCl
5. 5
   OtroThe organic layer was separated
6. 6
   Secadodried (Na2SO4)
7. 7
   Concentraciónconcentrated under reduced pressure
8. 8
   OtroPurification by flash column chromatography (methylene chloride/EtOAc, 15:1)

Procedimiento

To a solution of 2-fluoro-4-(methylthio)aniline (0.236 g, 1.50 mmol) in THF (10 mL) at −78° C. under N2 was added lithium bis(trimethylsilyl)amide (3.42 ml, 3.42 mmol, 1 M solution in hexanes) dropwise. The reaction mixture was stirred for one hour at −78° C. after the addition was complete. Methyl 2-chloro-5-fluoro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate (0.300 g, 1.37 mmol) was then added dropwise as a solution in THF (5 mL) and the reaction mixture was stirred for 30 minutes at −78° C. The reaction was quenched by the addition of 1 M HCl until the pH of the reaction mixture was 5, and then diluted with EtOAc and saturated NaCl. The organic layer was separated, dried (Na2SO4), and concentrated under reduced pressure. Purification by flash column chromatography (methylene chloride/EtOAc, 15:1) gave pure desired product (0.359 g, 75%) as a white solid.

Fuente