反应详情

温度

80 °C

A solution of methyl 2,5-dichloronicotinate (8.2 g, 40 mmol), (3-fluorophenyl)boronic acid (6.1 g, 44 mmol), and potassium carbonate (12 g, 86 mmol) in water (71 mL) and 1,4-dioxane (190 mL) was degassed with nitrogen (10 minutes). The reaction mixture was treated with bis(triphenylphosphine)palladium(II) chloride (3.1 g, 4.4 mmol), degassed with nitrogen (10 minutes), and heated at 80° C. for 14.5 hours. The reaction mixture was diluted with ethyl acetate and water and filtered over celite. The aqueous layer was separated and re-extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried with magnesium sulfate, filtered, and concentrated to a crude residue. Purification by flash column chromatography using ethyl acetate in hexanes (0-80%) gave the desired product (8.7 g, 83%). LCMS calculated for C13H10ClFNO2 (M+H)+: m/z=266.0. found: 265.8.

1. customdegassed with nitrogen (10 minutes)
2. additionThe reaction mixture was diluted with ethyl acetate and water
3. filtrationfiltered over celite
4. customThe aqueous layer was separated
5. extractionre-extracted with ethyl acetate
6. washThe combined organic layers were washed with water and brine
7. dry with materialdried with magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated to a crude residue
10. customPurification by flash column chromatography