反应详情

温度

130 °C

N,N-Dimethylformamide dimethylacetal (6.3 ml, 45 mmol) was added in one portion to a stirred solution of 3-chloro-4-fluoro-6-methylnitrobenzene (7.0 g, 37 mmol) in N,N-dimethylformamide (30 mL) at 130° C. under Ar. The mixture was stirred at 130° C. for 2 h, cooled to room temperature, concentrated in vacuo and partitioned between ethyl acetate and water and the aqueous was extracted with ethyl acetate (2×). The combined organic extracts were washed with brine, dried (magnesium sulfate), concentrated in vacuo, dissolved in methanol/tetrahydrofuran (1:1; 100 mL) and Raney Nickel®, 50% wt. in water, (5 g) was added. The mixture was cooled to 0° C. and hydrazine hydrate (3 mL, 59 mmol) was added dropwise over 2 min. The mixture was warmed to room temperature, stirred for 1 h then cooled to 0° C. and hydrazine hydrate (1.5 mL) was added over 2 min. The mixture was warmed to room temperature, stirred for 1 h and filtered through celite®. The filter-cake was washed with tetrahydrofuran and the filtrate was concentrated in vacuo and purified by column chromatography [SiO2; heptane-dichloromethane (4:1)] to give the product (3.2 g, 51%) as an off-white solid. An analytical sample was recrystallised (heptane) to give a white solid: mp 105-107° C.; NMR δH (400 MHz, CDCl3) 8.01 (1H, br. s), 7.40 (1H, d, J 6 Hz), 7.35 (1H, d, J 9.4 Hz), 7.25 (1H, t, J 2.8 Hz), 6.50-6.51 (1H, m).

1. temperaturecooled to room temperature
2. concentrationconcentrated in vacuo
3. custompartitioned between ethyl acetate and water
4. extractionthe aqueous was extracted with ethyl acetate (2×)
5. washThe combined organic extracts were washed with brine
6. dry with materialdried (magnesium sulfate)
7. concentrationconcentrated in vacuo
8. dissolutiondissolved in methanol/tetrahydrofuran (1:1; 100 mL)
9. additionRaney Nickel®, 50% wt. in water, (5 g) was added
10. temperatureThe mixture was cooled to 0° C.
11. temperatureThe mixture was warmed to room temperature
12. stirringstirred for 1 h
13. temperaturethen cooled to 0° C.
14. temperatureThe mixture was warmed to room temperature
15. stirringstirred for 1 h
16. filtrationfiltered through celite®
17. washThe filter-cake was washed with tetrahydrofuran
18. concentrationthe filtrate was concentrated in vacuo
19. custompurified by column chromatography [SiO2; heptane-dichloromethane (4:1)]