反应详情

温度

110 °C

Under nitrogen atmosphere, pyrrolidin-2-one (375 mg, 4.4 mmol), dimethylbisdiphenyl-phosphinoxanthene (CAS 161265-03-8, 127 mg, 2.4 mmol), tris(dibenzylideneacetone)dipalladium (CAS 51364-51-3, 67 mg, 0.1 mmol) and cesium carbonate (CAS 534-17-8, 1.8 g, 6 mmol) in 1,4-dioxane (100 mL) were added to a solution of 5-bromo-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (Example 9 d, 1 g, 4 mmol) and the reaction mixture was stirred overnight at 110° C. The reaction mixture was concentrated in vacuo, dissolved in water and extracted with ethyl acetate (3×30 mL). The aqueous layer was adjusted to pH=2 with aqueous solution of hydrochloride (1N), the resulting precipitate was collected by filtration and dried. The crude product was purified by column chromatography (silica gel, 20 g, eluting with 30% ethyl acetate in petroleum ether) to give the desired product (600 mg) as a yellow solid; MS (EI): m/e=277.1 [M+H]+.

1. concentrationThe reaction mixture was concentrated in vacuo
2. dissolutiondissolved in water
3. extractionextracted with ethyl acetate (3×30 mL)
4. filtrationthe resulting precipitate was collected by filtration
5. customdried
6. customThe crude product was purified by column chromatography (silica gel, 20 g, eluting with 30% ethyl acetate in petroleum ether)