تفاعل #11773

معادلة التفاعل

(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

المذيبات

toluene

toluene

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةheated
2. 2
   درجة الحرارةto reflux overnight
3. 3
   أخرىThe resulting reaction mixture
4. 4
   درجة الحرارةwas cooled to ambient temperature
5. 5
   أخرىquenched with water
6. 6
   استخلاصextracted with ethyl acetate
7. 7
   غسيلThe organic layer was washed with saturated aqueous sodium hydrogen carbonate
8. 8
   تجفيفdried over magnesium sulfate
9. 9
   ترشيحfiltered
10. 10
    تركيزconcentrated in vacuo

الإجراء التجريبي

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).

المصدر