反应详情

温度

50 °C

Add potassium trimethylsilanolate (0.651 g, 4.56 mmol, 90% purity) in one portion to a solution of 4-[(trimethylsilanyl)ethynyl]pyridine (40.0 g, 228 mmol, Ziessel, R., et al. J. Org. Chem. 1996, 61, 6535) and bis(tributyltin) oxide (95.2 g, 160 mmol) in THF (400 mL) while keeping the temperature between 25-30° C. with a water bath. After approximately 1 hour, concentrate the solution by rotary evaporation (50° C.) to give an oil containing 78-85% 4-[(tributylstannanyl)ethynyl]pyridine, 15-22% 4-ethynylpyridine and excess bis(tributyltin) oxide. Add 1-azidomethyl-3,5-bis(trifluoromethyl)benzene (73.7 g, 274 mmol) to the oil and heat at 110° C., distilling off any volatiles required to achieve the desired temperature. Heat the solution until the reaction is complete by 1H-NMR analysis (approximately 22 h). After cooling to 50° C., dilute the reaction mixture with heptane (600 mL) and stir at room temperature. Filter the mixture to remove the solids. Purify the mixture by pouring the heptane solution on a silica gel column (810 g silica gel in a 2 L fritted-glass funnel) and elute sequentially with heptane (5.2 L), 1:10 EtOAc:heptane (5.1 L), and 1:3 EtOAc:heptane (12.6 L). Combine the fractions containing product and concentrate by rotary evaporation to give 124 g (82% yield) of the title compound; mp 61.9-63.1° C.; Analysis for C28H36F6N4Sn: Calcd: C, 50.86; H, 5.49; N, 8.47. Found: C, 51.08, H, 5.61; N, 8.50.

1. custombetween 25-30° C.
2. concentrationconcentrate the solution
3. customby rotary evaporation (50° C.)
4. customto give an oil
5. distillationdistilling off any volatiles
6. temperatureHeat the solution until the reaction
7. customis complete by 1H-NMR analysis (approximately 22 h)
8. additiondilute the reaction mixture with heptane (600 mL)
9. filtrationFilter the mixture
10. customto remove the solids
11. customPurify the mixture
12. additionby pouring the heptane solution on a silica gel column (810 g silica gel in a 2 L fritted-glass funnel)
13. washelute sequentially with heptane (5.2 L), 1:10 EtOAc
14. additionCombine the fractions containing product
15. concentrationconcentrate by rotary evaporation