反応 #60280

反応方程式

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

K2CO3

methyl vinyl sulfone

→

pure desired product

収率 59.1%

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carboxylic acid methyl ester

収率 59.1%

溶媒

DMF

ethyl acetate

water

反応条件

後処理

1. 1
   その他The layers are separated
2. 2
   洗浄the organic layer is washed with water (3×) and brine
3. 3
   抽出The combined aqueous washes are extracted with ethyl acetate
4. 4
   乾燥The combined organic extracts are dried (MgSO4)
5. 5
   濃縮concentrated under reduced
6. 6
   その他Purification
7. 7
   workup.DISSOLUTIONby dissolving the residue in methylene chloride
8. 8
   その他precipitating with diethyl ether

実験手順

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester 8b (1.55 g, 3.89 mmol) is dissolved in 15 mL DMF under N2. K2CO3 (0.70 g, 5.06 mmol) is added followed by methyl vinyl sulfone (0.41 mL, 4.67 mmol). After stirring 16 hours at room temperature, the reaction mixture is diluted with ethyl acetate and water. The layers are separated and the organic layer is washed with water (3×) and brine. The combined aqueous washes are extracted with ethyl acetate. The combined organic extracts are dried (MgSO4) and concentrated under reduced. Purification by dissolving the residue in methylene chloride and precipitating with diethyl ether, repeated several times, provides 1.16 g (59%) pure desired product as a yellow solid: MS APCI (+) m/z 506, 504 (M+Br pattern) and 400, 398 (M−methyl ethyl sulfone Br pattern).

出典