تفاعل #60280

معادلة التفاعل

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

K2CO3

methyl vinyl sulfone

→

pure desired product

المردود 59.1%

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

المردود 59.1%

المذيبات

DMF

ethyl acetate

water

ظروف التفاعل

المعالجة

1. 1
   أخرىThe layers are separated
2. 2
   غسيلthe organic layer is washed with water (3×) and brine
3. 3
   استخلاصThe combined aqueous washes are extracted with ethyl acetate
4. 4
   تجفيفThe combined organic extracts are dried (MgSO4)
5. 5
   تركيزconcentrated under reduced
6. 6
   أخرىPurification
7. 7
   workup.DISSOLUTIONby dissolving the residue in methylene chloride
8. 8
   أخرىprecipitating with diethyl ether

الإجراء التجريبي

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).

المصدر