反应详情

温度

120 °C

A mixture containing 4-(4-aminobenzoyl)benzonitrile (1.30 g, 5.85 mmol, Intermediate 16: step c), 2-(4-(1H-1,2,4-triazol-1-yl)benzyl)malonic acid (1.53 g, 5.85 mmol, Intermediate 82: step c), and phosphorus oxychloride (6.5 mL) was heated to 120° C. After 105 minutes, the flask was allowed to cool to 23° C. Dichloromethane (50 mL) and ice (50 mL) were added and the resulting mixture cooled in an ice-water bath. 6 M aqueous potassium hydroxide solution was added dropwise with stirring until the pH was between 8-9 by litmus paper test. The biphasic mixture was allowed to warm to 23° C. and then the layers were separated. The aqueous layer was extracted with dichloromethane (50 mL). The organic layers were combined and the combined solution was dried over sodium sulfate. The dried solution was filtered. Silica gel (7 g) was added to the filtrate and then the solvents were removed by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a column of silica gel for purification. Elution with hexanes initially, grading to 75% ethyl acetate-hexanes provided the title compound as an impure yellow solid. The yellow solid was suspended in acetonitrile (30 mL). The suspension was sonicated at 23° C. After 10 minutes, the solids were collected by filtration and rinsed with acetonitrile. The collected solids were dried to provide pure title compound as a pale-yellow solid.

1. temperatureto cool to 23° C
2. temperaturethe resulting mixture cooled in an ice-water bath
3. temperatureto warm to 23° C.
4. customthe layers were separated
5. extractionThe aqueous layer was extracted with dichloromethane (50 mL)
6. dry with materialthe combined solution was dried over sodium sulfate
7. filtrationThe dried solution was filtered
8. additionSilica gel (7 g) was added to the filtrate
9. customthe solvents were removed by rotary evaporation
10. customto afford a free-flowing powder
11. customThe powder was loaded onto a column of silica gel for purification
12. washElution with hexanes initially