反应详情

温度

98 °C

To a 25 mL pressure resistant vial which contained a solution of the product from step 1 (44 mg, 0.25 mmol) and the product from step 2 (130 mg, 0.33 mmol) in anhydrous dioxane (4 mL) were added cesium carbonate (300 mg, 1.5 mmol) and N,N-dimethylglycine.HCl (25 mg, 0.66 mmol) at rt. The reaction mixture was flushed with argon and copper (I) iodide (14 mg, 0.06 mmol) was added. The vial was sealed and the reaction mixture was stirred at 98° C. for 72 h. After cooling to rt, the mixture was poured onto 50 mL ice-water solution and this solution was extracted with EtOAc (3×20 mL). The combined organic layers were washed with water (2×20 mL), brine (20 mL) and dried over anhydrous Na2SO4. The solvent was removed in vacuo to obtain the crude product which was purified by silica gel flash chromatography to afford the title product (80 mg, 70%); LCMS; 100%, APCI+ Calcd: 451.6, found m/z: 451.6 (M); 1H NMR (400 MHz, CDCl3); δ 1.48 (s, 9H), 1.81-2.09 (m, 4H), 3.27-3.48 (m, 2H), 3.70-3.97 (m, 1H), 4.02-4.21 (m, 2H), 6.88-7.05. (m, 6H), 7.32-7.38 (m, 3H), 7.52 (d, J=8.8 Hz, 2H):

1. customat rt
2. additionwas added
3. customThe vial was sealed
4. temperatureAfter cooling to rt
5. extractionthis solution was extracted with EtOAc (3×20 mL)
6. washThe combined organic layers were washed with water (2×20 mL), brine (20 mL)
7. dry with materialdried over anhydrous Na2SO4
8. customThe solvent was removed in vacuo
9. customto obtain the crude product which
10. customwas purified by silica gel flash chromatography