反应详情

温度

88.5 °C

2-(2-Amino-5-bromo-pyridin-3-yloxymethyl)-benzonitrile (9.0 g, 26.8 mmol), 4-carboxybenzeneboronic acid (4.9 g, 30.0 mmol), tetrakis(triphenylphosphine)-palladium(0) (1.1 g, 1.0 mmol), anhydrous potassium carbonate (13.1 g, 95 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 96° 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 0.8, product at Rf 0.5 and an impurity at Rf 0.4. The mixture was cooled to 45° C. and filtered to remove the solids. 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 4 g of Celite and 2 g of Norit were added. The solids were collected by vacuum filtration through 4 g of Celite, washed with 30 mL of ethanol:water 1:1 and discarded The filtrate was cooled in an ice bath and 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 8.1 g (80% yield) 4-[6-amino-5-(4-tert-butyl-benzyloxy)-pyridin-3-yl]-benzoic acid as a 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. filtrationfiltered
5. customto remove the solids
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. addition4 g of Celite and 2 g of Norit were added
9. filtrationThe solids were collected by vacuum filtration through 4 g of Celite
10. washwashed with 30 mL of ethanol:water 1:1
11. temperaturewas cooled in an ice bath
12. filtrationThe solids were collected by vacuum filtration
13. washwashed with 20 mL water
14. customdried under vacuum