반응 #60277

반응 방정식

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

수율 100.0%

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

수율 100.0%

용매

water

HCl

ethyl acetate tetrahydrofuran

water

반응 조건

후처리

1. 1
   workup.ADDITIONis added (2.5 mL)
2. 2
   온도The 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
   기타the layers separated
6. 6
   추출The aqueous layer is extracted with ethyl acetate
7. 7
   세척The combined organic layers are washed with brine
8. 8
   건조dried (Na2SO4)
9. 9
   농축concentrated under reduced pressure

실험 절차

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.

출처