反应详情

温度

85.5 °C

2-(2-Amino-5-bromo-pyridin-3-yloxymethyl)-benzonitrile (9.0 g, 29.6 mmol), 4-carboxybenzeneboronic acid (5.4 g, 32.5 mmol), tetrakis(triphenylphosphine)palladium(0) (1.1 g, 1.0 mmol), anhydrous potassium carbonate (13.8 g, 70.0 mmol), dimethylformamide (72 mL) and water (36 mL) were charged to a 250 mL three neck round bottom flask equipped with a thermometer, a reflux condenser and magnetic stirring. The mixture was purged with nitrogen and gradually heated from 81 to 90° C. over a period of 2 hr. Thin layer chromatography (ethyl acetate:hexane:acetic acid 4:6:0.5) showed a trace of starting material at Rf 0.7, product at Rf 0.4 and an impurity at Rf 0.5. The mixture was cooled to 45° C. The sticky solids were collected by vacuum filtration, washed with 30 mL of ethanol:water 1:1 and discarded. The filtrate was diluted with 432 mL of water and 8 mL of 9 N potassium hydroxide solution (to pH 12–13), cooled in an ice bath and stirred for 30 minutes. The solids were collected by vacuum filtration and washed with 20 mL of water. The solids were discarded. The filtrate was cooled in an ice bath acidified with acetic acid to pH 7.5 using a pH meter. The solids were collected by vacuum filtration, washed with 20 mL water and dried under vacuum to give 8.5 g (83% yield) of 4-[6-amino-5-(2-cyano-benzyloxy)-pyridin-3-yl]-benzoic acid as a very dark solid.

1. customequipped with a thermometer, a reflux condenser and magnetic stirring
2. customThe mixture was purged with nitrogen
3. temperatureThe mixture was cooled to 45° C
4. filtrationThe sticky solids were collected by vacuum filtration
5. washwashed with 30 mL of ethanol:water 1:1
6. additionThe filtrate was diluted with 432 mL of water and 8 mL of 9 N potassium hydroxide solution (to pH 12–13)
7. temperaturecooled in an ice bath
8. filtrationThe solids were collected by vacuum filtration
9. washwashed with 20 mL of water
10. temperatureThe filtrate was cooled in an ice bath
11. filtrationThe solids were collected by vacuum filtration
12. washwashed with 20 mL water
13. customdried under vacuum