反应详情

温度

0 °C

Sodium hydride (47.2 g, 1.18 mol) was suspended in 320 mL DMSO and cooled to 0° C. in an ice-water bath. The mixture became viscous as the DMSO began to freeze. Methyl cyanoacetate (104 mL, 1.18 mol) was added slowly causing a slight temperature increase and thus a more easily stirrable solution. The mixture was stirred for 30 minutes at room temperature. 4-Bromo-2-fluorobenzonitrile (118 g, 590 mmol) (commercially available from Acros Organics (Order Number 29049)) was added via cannula as a solution in 500 mL DMSO. The mixture was heated to an internal temperature of 90° C. The mixture was cooled and allowed to stand overnight. 1.2 L of water was added to the reaction mixture. The mixture was heated to an internal temperature of 104° C. over 3 hours. 2.3 L of water was added and the mixture was heated at reflux 16 hours. The mixture was cooled to 5° C. and 700 mL of 0.2N HCl was added. The mixture was allowed to stir at 5° C. for 30 minutes. The resulting precipitate was filtered, washed with water, and dried to provide the product (102 g, 78%). LCMS (API-ES) m/z: 223, 221 (M+H+).

1. temperatureincrease
2. temperatureThe mixture was heated to an internal temperature of 90° C
3. temperatureThe mixture was cooled
4. waitto stand overnight
5. temperatureThe mixture was heated to an internal temperature of 104° C. over 3 hours
6. temperaturethe mixture was heated
7. temperatureat reflux 16 hours
8. temperatureThe mixture was cooled to 5° C.
9. stirringto stir at 5° C. for 30 minutes
10. filtrationThe resulting precipitate was filtered
11. washwashed with water
12. customdried