Réaction #44218

Équation de réaction

lithium bis(trimethylsilyl)amide

2-(2-fluoro-4-methylphenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (2-vinyloxyethoxy)-amide

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

O-(2-vinyloxy-ethyl)-hydroxylamine

→

pure desired product

Rendement 77.0%

2-(2-Fluoro-4-methylphenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (2-hydroxyethoxy)-amide

Rendement 77.0%

Solvants

THF

Conditions de réaction

Traitement

1. 1
   TempératureThe reaction mixture was warmed to room temperature
2. 2
   Autrethe reaction mixture was quenched by the addition of NaHCO3
3. 3
   Autrepartitioned between EtOAc and saturated NaCl
4. 4
   AutreThe layers were separated
5. 5
   SéchageThe combined organic extracts were dried (Na2SO4)
6. 6
   Concentrationconcentrated under reduced pressure
7. 7
   AutrePurification by flash column chromatography (methylene chloride/methanol, 20:1)

Mode opératoire

Preparation of 2-(2-fluoro-4-methylphenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (2-vinyloxyethoxy)-amide: To a solution of 2-(2-fluoro-4-methylphenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid methyl ester (0.050 g, 0.17 mmol) in THF (1.5 mL) under N2 was added O-(2-vinyloxy-ethyl)-hydroxylamine (0.044 g, 0.43 mmol). The solution was cooled to 0° C. and lithium bis(trimethylsilyl)amide (0.86 mL, 0.86 mmol, 1 M solution in hexanes) was added dropwise. The reaction mixture was warmed to room temperature. After stirring for 40 minutes, the reaction mixture was quenched by the addition of NaHCO3 and partitioned between EtOAc and saturated NaCl. The layers were separated and the aqueous layer was reextracted with EtOAc. The combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure. Purification by flash column chromatography (methylene chloride/methanol, 20:1) gave 0.048 g (77%) pure desired product as an off-white foamy solid.

Source