反应详情

温度

68 °C

3-Bromo-2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridine (1 equiv), 3,4-dihydro-2H-pyran (2 equiv) and methanesulfonic acid (0.1 equiv) were combined in tetrahydrofuran, while stirring under nitrogen. The reaction was heated to 68° C. for 3.5 h. After cooling to room temperature over 1 h, triethylamine (0.4 equiv) was added and the resulting solution was stirred 10 min and then concentrated under reduced pressure. Acetonitrile was added and excess tetrahydrofuran was removed by codistillation under reduced pressure, with heating to 35° C. (twice). The resulting residue was dissolved in acetonitrile (1 volume) and water (2.25 volumes) was added. The resultant suspension was stirred 30 min. Solids were collected by filtration, washed with a solution of 20% acetonitrile in water and dried under reduced pressure. The crude product was triturated with hexanes, filtered, further washed with hexanes and dried in a vacuum oven at 35° C. to provide the desired product in 80% yield, as an off white solid. MS (ESI) m/z 324.9 [M+2]+.

1. temperatureAfter cooling to room temperature over 1 h
2. stirringthe resulting solution was stirred 10 min
3. concentrationconcentrated under reduced pressure
4. additionAcetonitrile was added
5. customexcess tetrahydrofuran was removed by codistillation under reduced pressure
6. temperaturewith heating to 35° C. (twice)
7. dissolutionThe resulting residue was dissolved in acetonitrile (1 volume)
8. additionwater (2.25 volumes) was added
9. stirringThe resultant suspension was stirred 30 min
10. filtrationSolids were collected by filtration
11. washwashed with a solution of 20% acetonitrile in water
12. customdried under reduced pressure
13. customThe crude product was triturated with hexanes
14. filtrationfiltered
15. washfurther washed with hexanes
16. customdried in a vacuum oven at 35° C.