Реакция #44218

Уравнение реакции

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

Выход 77.0%

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

Выход 77.0%

Растворители

THF

Условия реакции

Обработка

1. 1
   ТемператураThe reaction mixture was warmed to room temperature
2. 2
   Другоеthe reaction mixture was quenched by the addition of NaHCO3
3. 3
   Другоеpartitioned between EtOAc and saturated NaCl
4. 4
   ДругоеThe layers were separated
5. 5
   СушкаThe combined organic extracts were dried (Na2SO4)
6. 6
   Концентрированиеconcentrated under reduced pressure
7. 7
   ДругоеPurification by flash column chromatography (methylene chloride/methanol, 20:1)

Методика

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.

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