Reaktion #85481

Reaktionsgleichung

BOP

diisopropylethylamine

1-(1-methylpiperidin-4-yl)piperazine

[5-chloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-2,3-dihydro-1H-indol-3-yl]acetic acid

NaOH

→

title compound

Ausbeute 83.3%

5-Chloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-3-{2-[4-(1-methylpiperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-1,3-dihydroindol-2-one

Ausbeute 83.3%

Lösungsmittel

dichloromethane

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGwas stirred at room temperature for 15 minutes
2. 2
   SonstigeThe phases were separated
3. 3
   Extraktionthe aqueous phase was extracted with ethyl acetate (1×)
4. 4
   WaschenThe combined organic phase was again washed with water (1×) and saturated sodium chloride solution (1×)
5. 5
   Trocknendried over magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Sonstigethe solvent was evaporated in vacuo
8. 8
   SonstigeThe residue was purified by chromatography on silica gel (Redisep cartridge, mobile phase gradient from 2 to 50% methanol in dichloromethane)

Vorschrift

200 mg (0.45 mmol) of BOP, 1.07 ml (6.17 mmol) of diisopropylethylamine and then 79 mg (0.43 mmol) of 1-(1-methylpiperidin-4-yl)piperazine were added to a solution of 150 mg (0.41 mmol) of [5-chloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-2,3-dihydro-1H-indol-3-yl]acetic acid in 2 ml of dichloromethane. The reaction mixture was stirred at room temperature overnight. 6 ml of a 2-molar NaOH were added to the reaction solution, and it was stirred at room temperature for 15 minutes. The reaction mixture was diluted with ethyl acetate. The phases were separated and the aqueous phase was extracted with ethyl acetate (1×). The combined organic phase was again washed with water (1×) and saturated sodium chloride solution (1×), dried over magnesium sulfate and filtered, and the solvent was evaporated in vacuo. The residue was purified by chromatography on silica gel (Redisep cartridge, mobile phase gradient from 2 to 50% methanol in dichloromethane). 181 mg of the title compound were obtained as a white solid.

Quelle