4-bromo-2-fluoro-6-methylbenzamide

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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. under reflux in an inert (nitrogen) environment for about 24 h Layers were separated the organic phase was washed with brine filtered to remove particulate material The extract was concentrated under reduced pressure to about 30 ml to obtain a slurry heated to reflux to dissolve all solids The resulting solution cooled slowly to room temperature 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

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-bromo-2-fluoro-6-methyl benzoic acid (200 g) was dissolved in 1 L of THF and treated portion wise with carbonyldiimidazole (180 g, 1.3 eq). The reaction mixture is stirred at ambient temperature for about 3 hours and then quenched by addition of aqueous ammonium hydroxide (400 ml). The resulting reaction mixture was stirred overnight at ambient temperature and then concentrated under reduced pressure to about 0.5 L volume. The resulting slurry was diluted by adding 1 L of water. The precipitated product was isolated by filtration, washed with water (3×300 ml), dried under vacuum at about 60° C. to obtain 174 g (87% isolated yield) of product. quenched by addition of aqueous ammonium hydroxide (400 ml) The resulting reaction mixture was stirred overnight at ambient temperature concentrated under reduced pressure to about 0.5 L volume The resulting slurry was diluted by adding 1 L of water The precipitated product was isolated by filtration washed with water (3×300 ml) dried under vacuum at about 60° C. to obtain 174 g (87% isolated yield) of product