反应详情

Under a nitrogen atmosphere, a solution of 5-bromo-6-(cyclopropylmethoxy)-pyridine-2-carboxylic acid methyl ester (Example 114 a, 1 g, 3.5 mmol), bis(2,2,2-trifluoroethyl)amine (1.90 g, 10 mmol), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (CAN 98327-87-8, 0.435 g, 1 mmol), tris(dibenzylideneacetone) dipalladium (CAN 51364-51-3, 0.32 g, 0.35 mmol) and cesium carbonate (CAN 534-17-8, 3.4 g, 10 mmol) in toluene (50 mL) was reacted overnight at 110° C. The reaction mixture was concentrated under reduced pressure, dissolved in water, extracted with ethyl acetate (50 mL), the aqueous layer was adjusted to pH 2 with conc. HCl, then extracted with ethyl acetate (3×50 mL), washed with brine (2×50 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 10 g, 20% ethyl acetate in petroleum ether) to yield the title compound (0.5 g, 29.7%) as a yellow oil; MS: m/e=387.1 [M+H]+.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutiondissolved in water
3. extractionextracted with ethyl acetate (50 mL)
4. extractionextracted with ethyl acetate (3×50 mL)
5. washwashed with brine (2×50 mL)
6. dry with materialdried over Na2SO4
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by column chromatography (silica gel, 10 g, 20% ethyl acetate in petroleum ether)