反应详情

温度

110 °C

Charge a flask with trifluoromethanesulfonic acid 6-methanesulfonyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (8.8 g, 14.6 mmol) and 3,5-difluoro-2-methylsulfanyl-benzene boronic acid (9.0 g, 42 mmol) and flush with nitrogen. Dissolve solids in degassed dioxane (240 mL). Add 2M sodium carbonate (120 mL) and Pd(PPh3)4 (6.7 g, 5.9 mmol). Plunge into 110° C. oil bath and stir vigorously. After 30 minutes, cool the reaction to room temperature and filter off solids. Partition the filtrate between water and methylene chloride. Wash the organic layer with water twice, dry over sodium sulfate, filter and concentrate. Purify the residue over silica gel, eluting with 1 to 2% methanol in methylene chloride, to yield 8.0 g (90%) of the title compound. LCMS Rt (0.01% heptafluorobutyric acid:1.0% isopropylalcohol:water is mobile phase A and 0.01% heptafluorobutyric acid:1.0% isopropylalcohol:acetonitrile is mobile phase B; gradient method 25 to 95% B, Purity@254 nm)=3.18 mm (99%); mass spectrum (ion spray): m/z=612.3 (M+H).

1. customflush with nitrogen
2. dissolutionDissolve solids in degassed dioxane (240 mL)
3. temperaturecool
4. customthe reaction to room temperature
5. filtrationfilter off solids
6. customPartition the filtrate between water and methylene chloride
7. washWash the organic layer with water twice
8. dry with materialdry over sodium sulfate
9. filtrationfilter
10. concentrationconcentrate
11. customPurify the residue over silica gel
12. washeluting with 1 to 2% methanol in methylene chloride