反应详情

tert-Butyl isocyanide (301 mg, 0.41 mL, 3.6 mmol) was added to a stirred slurry of 1-[4-(4-chlorophenyl)-cyclohexyl]pent-4-en-1-one (800 mg, 2.9 mmol) and ammonium acetate (671 mg, 8.7 mmol) in 2,2,2-trifluoroethanol (0.4 mL). After stirring at room temperature for 8 days, the reaction mixture was poured into water and extracted with ethyl acetate (3×). The combined organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (silica gel, 10-50% ethyl acetate in heptane) gave 2-acetamido-N-tert-butyl-2-(4-(4-chlorophenyl)cyclohexyl)hex-5-enamide as a colorless oil (940 mg, 77%); 1H NMR (CDCl3, 300 MHz) δ 7.24 (m, 2H), 7.15 (m, 2H), 7.04 (br s, NH, 1H), 5.80 (m, 1H), 5.544 (br s, NH, 1H), 4.97 (m, 2H), 3.04 (ddd, J1=14 Hz, J2=11.5 Hz, J3=5.0 Hz, 1H), 2.38 (tt, J1=12 Hz, J2=2 Hz, 1H), 2.28 (tt, J1=12 Hz, J2=2 Hz, 1H), 2.03 (s, 3H), 1.68-1.95 (m, 5H), 1.42-1.61 (m, 4H), 1.41 (s, 9H), 1.26 (m, 1H) and 1.12 (m, 1H); MS (+CI): m/z for C24H35ClN2O2: expected 418.2. found 419.2 (M+H)+.

1. extractionextracted with ethyl acetate (3×)
2. washThe combined organic phase was washed with saturated aqueous sodium chloride
3. dry with materialdried over anhydrous magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customPurification by flash column chromatography (silica gel, 10-50% ethyl acetate in heptane)