反应详情

温度

-10 °C

(2-Trityltetrazol-5-yl)benzene (25.0 g) was dissolved in dry THF (250 mL) and the solution of the tetrazole was cooled to -20° C. and n-butyllithium (28.3 mL, 2.5M in hexanes) was added. The mixture was gradually warmed to -10° C. over 1 hour and then aged at this temperature for an additional 30 minutes. A 1.4M THF solution of zinc chloride (51.3 mL) was then added to the aryllithium reagent prepared above while maintaining the lithium reagent solution at ≤0° C. In another flask an activated nickel catalyst solution was prepared as follows. To a solution of (PPh3)2NiCl2 (2.5 g) in THF (35 mL) at 0° C. was added methylmagnesium chloride (2.5 mL, 3M in THF) followed by p-iodotoluene (17.5 g). The catalyst solution was warmed to 20° C. and the solution of the zinc reagent was added at a rate that maintained the reaction temperature between 20° to 25° C. Ten hours after the addition of the zinc reagent to the reaction was complete, the reaction mixture was cooled to 0° C., 8.0 g of SuperCel (filter aid) was added, followed by the addition of concentrated ammonium hydroxide (15 mL) over 30 minutes. The heterogeneous solution was aged at 0° C. for 1 hour and filtered. The filter cake was washed with THF (50 mL). The filtrate was washed with a mixture of saturated NaCl (80 mL) and saturated NaHCO3 (30 mL) and the layers separated. The THF layer was dried with anhydrous Na2CO3 (30 g) and filtered. The volume of the filtrate was reduced to 150 mL and cyclohexane (300 mL) was added. The THF was further distilled in vacuo while the temperature of the mixture was maintained at 40° to 45° C. Cyclohexane was added periodically to maintain the volume at 200 mL. When the amount of THF dropped to ≤3 percent, the distillation was stopped and the mixture was cooled to room temperature. Hexanes (150 mL) was then added and the mixture further aged at 0° C. for 1 hour. The product was collected and washed with hexanes (100 mL). The yield was 28.8 g (94%).

1. customprepared above
2. temperatureThe catalyst solution was warmed to 20° C.
3. temperaturethat maintained the reaction temperature between 20° to 25° C
4. temperaturethe reaction mixture was cooled to 0° C.
5. filtration8.0 g of SuperCel (filter aid)
6. additionwas added
7. additionfollowed by the addition of concentrated ammonium hydroxide (15 mL) over 30 minutes
8. waitThe heterogeneous solution was aged at 0° C. for 1 hour
9. filtrationfiltered
10. washThe filter cake was washed with THF (50 mL)
11. washThe filtrate was washed with a mixture of saturated NaCl (80 mL) and saturated NaHCO3 (30 mL)
12. customthe layers separated
13. dry with materialThe THF layer was dried with anhydrous Na2CO3 (30 g)
14. filtrationfiltered
15. additionwas added
16. distillationThe THF was further distilled in vacuo while the temperature of the mixture
17. temperaturewas maintained at 40° to 45° C
18. additionCyclohexane was added periodically
19. temperatureto maintain the volume at 200 mL
20. additionWhen the amount of THF dropped to ≤3 percent
21. distillationthe distillation
22. temperaturethe mixture was cooled to room temperature
23. additionHexanes (150 mL) was then added
24. waitthe mixture further aged at 0° C. for 1 hour
25. customThe product was collected
26. washwashed with hexanes (100 mL)