反应详情

温度

110 °C

2,4-Difluoro-6-methoxybenzonitrile (for a preparation see Intermediate 48) (29.2 g, 0.17 mol) was suspended in n-butanol (250 mL) and hydrazine hydrate (16.6 mL, 0.34 mol) was added. The suspension was heated at 110° C. for 19 h, then 115° C. for 4 h. The reaction was allowed to cool and a solid formed overnight. The solid was collected by filtration, and washed with n-butanol. Solid is mainly an aryl hydrazine by-product (uncyclised or regioisomer). The filtrate was concentrated and azeotroped with toluene to give 15.6 g of crude product (84% by LCMS). The crude product was taken up in ˜400 mL water, ˜5 mL AcOH and ˜350 mL ethyl acetate and any insoluble material was discarded. The organic layer was washed with water, dried (MgSO4) and evaporated. The residue was taken up in hot ethyl acetate (75 mL, 55° C.) and heptane was added (20 mL). The solid was collected by filtration, washed with heptane. This was repeated twice to give the title compound (6.7 g, 21%) as a purple solid.

1. temperatureto cool
2. customa solid formed overnight
3. filtrationThe solid was collected by filtration
4. washwashed with n-butanol
5. concentrationThe filtrate was concentrated
6. customazeotroped with toluene
7. customto give 15.6 g of crude product (84% by LCMS)
8. washThe organic layer was washed with water
9. dry with materialdried (MgSO4)
10. customevaporated
11. customwas taken up in hot ethyl acetate (75 mL, 55° C.)
12. additionheptane was added (20 mL)
13. filtrationThe solid was collected by filtration
14. washwashed with heptane