反应详情

温度

80 °C

To a solution of ethyl {(1S)-5-[3-(4-iodophenoxy)propoxy]-2,3-dihydro-1H-inden-1-yl}acetate (70 mg, 0.15 mmol, Example 94) in DMF (1 mL), was added bis(pinacolato)diboron (41 mg, 0.16 mmol), PdCl2(dppf).CH2Cl2 (11 mg, 0.01 mmol), and KOAc (43 mg, 0.44 mmol). Argon was passed through the solution, and the reaction mixture was heated at 80° C. for 2 h, and then cooled to rt. More PdCl2(dppf).CH2Cl2 (5 mg, 0.005 mmol) was added, followed by the addition of 2-bromo-6-methylpyridine (50 mg, 0.29 mmol) and Na2CO3 (2 M aqueous solution, 0.37 mL). The reaction mixture was heated to 80° C. for 12 h, after which the reaction mixture was cooled to rt, diluted with HCl (1N aqueous solution) and extracted with EtOAc. The combined organic phases were dried, filtered, and concentrated under reduced pressure. Purification by a preparative thin layer chromatography (2:3 EtOAc/hexanes) gave 286 mg (40%) of the title compound. 1H NMR (400 MHz, CDCl3): δ 8.00 (d, 2H), 7.73-7.62 (m, 1H), 7.62-7.52 (m, 1H), 7.16-6.96 (m, 4H), 6.83 (s, 1H), 6.52 (d, 1H), 4.28-4.04 (m, 6H), 3.52-3.38 (m, 1H), 2.96-2.63 (m, 3H), 2.54 (s, 3H), 2.48-2.12 (m, 4H), 1.82-1.62 (m, 1H), 1.23 (t, 3H).

1. temperaturecooled to rt
2. temperatureThe reaction mixture was heated to 80° C. for 12 h
3. temperatureafter which the reaction mixture was cooled to rt
4. extractionextracted with EtOAc
5. customThe combined organic phases were dried
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customPurification by a preparative thin layer chromatography (2:3 EtOAc/hexanes)