反应详情

温度

90 °C

To a solution of 1-[2-(4-bromo-phenyl)-(1R,2R)-cyclopropylmethyl]-(2R)-2-methyl-pyrrolidine (product of Example 3C, 50 mg, 0.17 mmol) in isopropyl alcohol (4 mL) under an atmosphere of nitrogen was added 4-cyanophenylboronic acid (30 mg, 0.2 mmol), dichlorobis(triphenylphosphine)palladium(II) (6 mg, 8.5 μmol) and potassium carbonate (59 mg, 0.43 mmol). The mixture was heated to 90° C. for 5 hours, cooled to ambient temperature and partitioned between ethyl acetate (25 mL) and H2O (10 mL). The organic extraction was washed with brine, dried (MgSO4), filtered, concentrated under reduced pressure and chromatographed on silica gel eluting with methanol (containing 10% concentrated NH4OH) in dichloromethane to provide the title compound 1H NMR (300 MHz, CD3OD) 1.08 (m, 1H), 1.19 (m, 1H), 1.32 (d, J=6 Hz, 3H), 1.42 (m, 1H), 1.63 (m, 1H), 1.99 (m, 3H), 2.20 (m, 1H), 2.65 (m, 1H), 2.94 (m, 1H), 3.07 (m, 1H), 3.34 (dd, J=9 Hz, J=6 Hz, 1H), 3.51 (m, 1H), 7.24 (d, J=9 Hz, 2H), 7.60 (d, J=6 Hz, 2H), 7.78 (s, 4H). MS (DCl—NH3) m/z 317 (M+H)+.

1. temperaturecooled to ambient temperature
2. custompartitioned between ethyl acetate (25 mL) and H2O (10 mL)
3. extractionThe organic extraction
4. washwas washed with brine
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customchromatographed on silica gel eluting with methanol (containing 10% concentrated NH4OH) in dichloromethane