反应详情

温度

60 °C

A mixture of 4-bromo-2-fluoro-6-methylbenzamide (10 g), cyclopropylboronic acid (4.87 g, 1.25 eq), tricyclohexylphosphine (725 mg, 0.06 eq), tris (dibenzyllideneacetone)dipalladium(0) chloroform adduct (446 mg, 0.01 eq) and potassium carbonate (17.9 g, 3 eq) in toluene (100 ml) and water (10 ml) was stirred under reflux in an inert (nitrogen) environment for about 24 h. The reaction mixture was then cooled to about 60° C. and treated with 10% aqueous ammonium hydroxide (60 ml) and then with ethyl acetate (60 ml). Layers were separated, the organic phase was washed with brine and filtered to remove particulate material. The extract was concentrated under reduced pressure to about 30 ml to obtain a slurry. This was diluted with heptane (80 ml) and ethyl acetate (20 ml) and then heated to reflux to dissolve all solids. The resulting solution cooled slowly to room temperature to allow the product to crystallize out. The precipitated product was isolated by filtration, washed with ethyl acetate-heptane (1:1) mixture (60 ml), dried under vacuum at about 60° C. to obtain 6.85 g (82.3% isolated yield) of product.

1. temperatureunder reflux in an inert (nitrogen) environment for about 24 h
2. customLayers were separated
3. washthe organic phase was washed with brine
4. filtrationfiltered
5. customto remove particulate material
6. concentrationThe extract was concentrated under reduced pressure to about 30 ml
7. customto obtain a slurry
8. temperatureheated
9. temperatureto reflux
10. dissolutionto dissolve all solids
11. temperatureThe resulting solution cooled slowly to room temperature
12. customto crystallize out
13. customThe precipitated product was isolated by filtration
14. washwashed with ethyl acetate-heptane (1:1) mixture (60 ml)
15. customdried under vacuum at about 60° C.
16. customto obtain
17. custom6.85 g (82.3% isolated yield) of product