反应详情

温度

65 °C

To a suspension of 3-bromo-2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridine (96.0 g, 0.4 mol) in tetrahydrofuran (780 mL) was added 3,4-dihydro-2H-pyran (72.5 mL, 0.8 mol) and methanesulfonic acid (3.2 mL). The mixture was heated to 65° C. and the resulting yellow solution was allowed to stir at 65° C. for 6 h. The mixture was cooled to ambient temperature, quenched with triethylamine (23 mL), concentrated under reduced pressure and further dried in a high vacuum for 1 h. The resulting oil was dissolved in acetonitrile (250 mL) and the solution was added into water (750 mL) while stirring vigorously. More acetonitrile (80 mL) was added and the mixture was allowed to stir for 1 h. The resulting solids were filtered, washed with 1:4 acetonitrile/water (800 mL) and dried in a vacuum oven for 48 h to afford the product (110 g, 85% yield) as a white solid. The product was further purified by silica gel plug purification (1:1 hexanes/ethyl acetate) to give 88 g of the pure product as a white solid and 16.2 g of less pure product. MS (ESI) m/z 239.1 [M]+, 241.1 [M+2]+.

1. temperatureThe mixture was cooled to ambient temperature
2. customquenched with triethylamine (23 mL)
3. concentrationconcentrated under reduced pressure
4. customfurther dried in a high vacuum for 1 h
5. dissolutionThe resulting oil was dissolved in acetonitrile (250 mL)
6. additionthe solution was added into water (750 mL)
7. stirringwhile stirring vigorously
8. additionMore acetonitrile (80 mL) was added
9. stirringto stir for 1 h
10. filtrationThe resulting solids were filtered
11. washwashed with 1:4 acetonitrile/water (800 mL)
12. customdried in a vacuum oven for 48 h