反应详情

N-[(3R,5S)-1-(Benzyloxy)-5-isopropyl-2-oxopyrrolidinyl]-4′-(trifluoromethyl)[1,1′-biphenyl]-4-sulfonamide (0.047 g, 0.088 mmoles, Example 27a), 1-iodopropane (0.052 mL, 0.53 mmoles), cesium carbonate (0.043 g, 0.13 mmoles) and anhydrous N,N-dimethylformamide (0.50 mL) was stirred at 55° C. (oil temperature) over night, concentrated by rotary evaporation, taken up diethylether and washed with water once. The aqueous phase was washed with a second portion of diethylether, the combined organic phases were washed with brine, dried with potassium carbonate, filtered and concentrated by rotary evaporation. Flash chromatography of the crude product on silica using dichloromethane-methanol (99:1) as eluent gave the title compound as a colourless oil. LC-MS (APCI) m/z 575 (M+1). 1H NMR (CDCl3) δ 8.12 (d, J=8 Hz, 2H), 7.74–7.69 (m, 5H), 7.72 (d, J=8 Hz, 2H), 7.44–7.34 (m, 4H), 5.01 (s, 2H), 4.48 (dd, J1=8 Hz, J2=10 Hz, 1H), 3.45 (dt, J1=3 Hz, J2=9 Hz, 1H), 3.10–2.98 (m, 2H), 2.24 (ddd, J1=2 Hz, J2=10 Hz, J3=14 Hz, 1H), 2.20–2.10 (m, 1H), 2.03 (dt, J1=9 Hz, J2=14 Hz, 1H), 1.73–1.51 (m, 2H), 0.87 (d, J=7 Hz, 3H), 0.84 (d, J=7 Hz, 3H) and 0.82 (obscured t, J=7 Hz, 3H) ppm.

1. concentrationconcentrated by rotary evaporation
2. washwashed with water once
3. washThe aqueous phase was washed with a second portion of diethylether
4. washthe combined organic phases were washed with brine
5. dry with materialdried with potassium carbonate
6. filtrationfiltered
7. concentrationconcentrated by rotary evaporation