تفاعل #44218

معادلة التفاعل

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

المردود 77.0%

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

المردود 77.0%

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe reaction mixture was warmed to room temperature
2. 2
   أخرىthe reaction mixture was quenched by the addition of NaHCO3
3. 3
   أخرىpartitioned between EtOAc and saturated NaCl
4. 4
   أخرىThe layers were separated
5. 5
   تجفيفThe combined organic extracts were dried (Na2SO4)
6. 6
   تركيزconcentrated under reduced pressure
7. 7
   أخرىPurification by flash column chromatography (methylene chloride/methanol, 20:1)

الإجراء التجريبي

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.

المصدر