反应详情

温度

90 °C

To a solution of 2-(4-bromo-2-fluorophenyl)-2-methylpropanenitrile (3.0 g, 12.4 mmol) in diisopropylamine (32 mL) and DMF (16 mL) was added 6-(2-cyclopentyl-2-hydroxybut-3-ynyl)-2,2-dimethyl-4H-1,3-dioxin-4-one (3.2 g, 12.4 mmol), PdCl2(PPh3)2 (350 mg, 4 mol %), CuI (71 mg, 3 mol %). The mixture was heated to 90° C. for 30 min before it was cooled down to room temperature. The reaction was diluted with aqueous NH4Cl, extracted with EtOAc (3×50 mL). The combined organic extracts were washed with brine, dried with Na2SO4 and evaporated to dryness. The mixture was purified by flash column chromatography (10–50% EtOAc in hexanes) to give the product (4.2 g, 79% yield). 1H NMR (300 MHz, CDCl3) δ: 1.65–1.76 (m, 14 H), 1.79 (s, 6 H), 1.82–1.85 (m, 1 H), 2.24 (s, 1 H), 2.59 (s, 1 H), 2.67 (m, 2 H), 5.46 (m, 1 H), 7.11 (dd, J=12.15, 1.60 Hz, 1 H), 7.18 (dd, J=8.10, 1.70 Hz, 1 H), 7.45 (t, J=8.10 Hz, 1 H).

1. temperaturewas cooled down to room temperature
2. extractionextracted with EtOAc (3×50 mL)
3. washThe combined organic extracts were washed with brine
4. dry with materialdried with Na2SO4
5. customevaporated to dryness
6. customThe mixture was purified by flash column chromatography (10–50% EtOAc in hexanes)