反应详情

Charge a flask with trifluoromethanesulfonic acid 6-methanesulfonyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (10.0 g, 16.6 mmol), 2-methylsulfanyl-4-fluoro-benzene boronic acid (7.7 g, 41.6 mmol), palladium acetate (371 mg, 1.66 mmol, tricyclohexylphosphine (700 mg, 2.5 mmol) and cesium fluoride (13 g, 83 mmol) and purge with nitrogen. Dilute with degassed acetonitrile (150 mL) and plunge into an 80° C. oil bath. Cool to room temperature after 1.5 hours and filter through celite and concentrate in vacuo. Partition the residue between methylene chloride and saturate aqueous sodium bicarbonate. Dry the organic layer with sodium sulfate, filter and concentrate. Purify the residue over a silica gel column, eluting with 2% methanol in methylene chloride, to yield 9.0 g (92%) 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)=2.92 min (95%); mass spectrum (ion spray): m/z=594.3 (M+H).

1. custompurge with nitrogen
2. additionDilute with degassed acetonitrile (150 mL) and plunge into an 80° C. oil bath
3. filtrationfilter through celite
4. concentrationconcentrate in vacuo
5. customPartition the residue between methylene chloride
6. concentrationsaturate aqueous sodium bicarbonate
7. dry with materialDry the organic layer with sodium sulfate
8. filtrationfilter
9. concentrationconcentrate
10. customPurify the residue over a silica gel column
11. washeluting with 2% methanol in methylene chloride