反应详情

温度

-78 °C

7-Fluoro-6-o-tolylamino-1H-benzoimidazole-5-carboxylic acid methyl ester 7a (2.00 g, 6.68 mmol) is suspended in 1:1 THF/MeOH (60 mL) and cooled to −78° C. under a nitrogen atmosphere. A solution of NBS (1.20 g, 6.75 mmol) in 1:1 THF/MeOH (5 mL) is added followed by a MeOH (5 mL) solution of TsOH.H2O (1.9 g, 10.0 mmol). After 30 minutes, the reaction mixture is warmed to 0° C. and then after 1 hour warmed to room temperature. After 16 hours, more NBS (0.12 g, 0.67 mmol) is added and the reaction mixture is allowed to stir for 3 hours. The reaction mixture is quenched by the addition of 10% Na2S2O4 solution. After 30 minutes, the reaction mixture is diluted with water and ethyl acetate and the layers separated. The aqueous layer is extracted with ethyl acetate. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. The recovered solid is triturated with methylene chloride to give 2.00 g (79%) pure desired product: MS APCI (+) m/z 380, 378 (M+1 Br pattern) detected.

1. temperaturethe reaction mixture is warmed to 0° C.
2. temperatureafter 1 hour warmed to room temperature
3. waitAfter 16 hours
4. customThe reaction mixture is quenched by the addition of 10% Na2S2O4 solution
5. waitAfter 30 minutes
6. additionthe reaction mixture is diluted with water and ethyl acetate
7. customthe layers separated
8. extractionThe aqueous layer is extracted with ethyl acetate
9. dry with materialThe combined organic extracts are dried (Na2SO4)
10. concentrationconcentrated under reduced pressure
11. customThe recovered solid is triturated with methylene chloride