Reaktion #60277

Reaktionsgleichung

LiOH

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(tetrahydro-pyran-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acid

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(tetrahydro-pyran-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acid methyl ester

tetrahydrofuran water

→

pure desired product

Ausbeute 100.0%

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(tetrahydro-pyran-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide

Ausbeute 100.0%

Lösungsmittel

water

HCl

ethyl acetate tetrahydrofuran

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONis added (2.5 mL)
2. 2
   TemperaturThe reaction mixture is cooled to 0° C.
3. 3
   workup.ADDITIONis added dropwise until the pH of the solution
4. 4
   workup.ADDITIONThe reaction mixture is poured into a separatory funnel
5. 5
   Sonstigethe layers separated
6. 6
   ExtraktionThe aqueous layer is extracted with ethyl acetate
7. 7
   WaschenThe combined organic layers are washed with brine
8. 8
   Trocknendried (Na2SO4)
9. 9
   Einengenconcentrated under reduced pressure

Vorschrift

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(tetrahydro-pyran-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acid 11 r: 6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(tetrahydro-pyran-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acid methyl ester 11q is suspended in 4:1 tetrahydrofuran/water (2.5 mL) and aqueous 1 M LiOH is added (2.5 mL). After stirring at room temperature for 16 hours, the reaction mixture is homogeneous and the reaction is complete. The reaction mixture is cooled to 0° C., diluted with water and aqueous 2 M HCl is added dropwise until the pH of the solution is 1-2, at which time it turns to a suspension. The reaction mixture is poured into a separatory funnel and diluted with ethyl acetate/tetrahydrofuran and water and the layers separated. The aqueous layer is extracted with ethyl acetate. The combined organic layers are washed with brine, dried (Na2SO4) and concentrated under reduced pressure to yield 0.11 g (100%) of the pure desired product as a white solid. MS ESI (+) m/z 482, 484 (M+, Br pattern) detected.

Quelle