Реакция #11773

Уравнение реакции

(2,5-dichloro-pyridin-3-yl)-acetic acid methyl ester

1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-hydroxy-ethanone

sodium hydride

→

title compound

(5-Chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-pyridin-3-yl)-acetic acid methyl ester

(5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-pyridin-3-yl)-acetic acid

Растворители

toluene

toluene

Условия реакции

Обработка

1. 1
   Температураheated
2. 2
   Температураto reflux overnight
3. 3
   ДругоеThe resulting reaction mixture
4. 4
   Температураwas cooled to ambient temperature
5. 5
   Другоеquenched with water
6. 6
   Экстракцияextracted with ethyl acetate
7. 7
   ПромывкаThe organic layer was washed with saturated aqueous sodium hydrogen carbonate
8. 8
   Сушкаdried over magnesium sulfate
9. 9
   Фильтрацияfiltered
10. 10
    Концентрированиеconcentrated in vacuo

Методика

To a 0° C. solution of (2,5-dichloro-pyridin-3-yl)-acetic acid methyl ester (0.45 g, 2.05 mmol) and 1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-hydroxy-ethanone (0.52 g, 1.86 mmol) in toluene (5.5 mL) was added sodium hydride (0.082 g, 2.05 mmol, 60% dispersion in mineral oil) in toluene (9.3 mL). The reaction mixture was slowly warmed to ambient temperature and then heated to reflux overnight. The resulting reaction mixture was cooled to ambient temperature, quenched with water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over magnesium sulfate, filtered and concentrated in vacuo. Chromatography on silica gel gave the title compound (0.14 g) and (5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-pyridin-3-yl)-acetic acid (0.20 g).

Источник