反应详情

温度

150 °C

To a solution of [3-(hydroxymethyl)phenyl]boronic acid (2 g, 13.2 mmol) in 1,4-dioxan (40 mL) was added [(3-bromo-4-fluorophenyl)methyl]amine hydrochloride (3.18 g, 13.2 mmol), potassium carbonate (9.1 g, 66 mmol) and tetrakis(triphenylphosphine)-palladium(0) (456 mg, 0.4 mmol). The mixture was split into 4×20 mL capacity microwave vials and each was treated with water (3 mL). The mixtures were each heated at 150° C. for 20 min. One sixth of the total reaction mixture was treated with water (100 mL) and extracted with ethyl acetate (2×80 mL). The combined organic phase was dried (magnesium sulphate) and concentrated to dryness and the product purified by flash chromatography on silica using 0-50% ethyl acetate/cyclohexane followed by dichloromethane/ammonia solution/methanol @ 8:1:1 as eluants. Product-containing fractions were combined and concentrated to dryness to afford 402 mg of the title compound. LC-MS m/z 463 (M+H)+, 0.65 min (ret time). The remaining five-sixth of the reaction mixture was worked up in the same manner and purified by flash chromatography using ethyl acetate/cyclohexane @ 1:1 followed by dichloromethane/ammonia solution/methanol @ 8:1:1 as eluants. This yielded 1.97 g of the title compound. LC-MS m/z 463 (M+H)+, 0.65 min (ret time).

1. customThe mixture was split into 4×20 mL capacity microwave vials
2. additioneach was treated with water (3 mL)
3. customOne sixth of the total reaction mixture
4. extractionextracted with ethyl acetate (2×80 mL)
5. dry with materialThe combined organic phase was dried (magnesium sulphate)
6. concentrationconcentrated to dryness
7. customthe product purified by flash chromatography on silica using 0-50% ethyl acetate/cyclohexane
8. concentrationconcentrated to dryness