反应详情

A solution of Example 11D (0.10 g, 0.210 mmol) in ethanol (3 mL) and H2O (3 mL) was treated with acetaldehyde (3 mL, 53.1 mmol) and stirred in a sealed microwave tube at room temperature for 73 hours. The solvent was removed in vacuo leaving a cloudy slurry which was dissolved in ethyl acetate (50 mL) and treated with 5% aqueous HCl (5 mL). The mixture was stirred for 30 minutes at room temperature. The aqueous layer was removed and the ethyl acetate layer was washed with 10 mL 10% aqueous NaCl, dried over anhydrous sodium sulfate (solid), filtered. The solvent was removed in vacuo leaving a clear yellow oil. Purification on a silica gel column (4 g) eluting with a gradient of 99.5/0.5 dichloromethane/methanol to 94/6 dichloromethane/methanol over 25 minutes afforded the title compound (0.021 g, 20%). 1H NMR (500 MHz, DMSO-d6) δ ppm 0.56 (s, 1H), 0.84 (m, 2H), 1.07 (dd, J=6.3, 4.5 Hz, 2H), 1.37 (dd, J=5.1, 2.1 Hz, 3H), 1.32-1.48 (m, 2H), 2.37 (ddd, J=12.7, 6.9, 5.5 Hz, 4H), 3.13 (s, 3H), 3.66 (m, 2H), 4.36 (t, J=5.1 Hz, 1H), 5.74-5.80 (m, 1H), 7.22 (s, 1H), 7.30 (s, 1H), 7.42 (t, J=8.9 Hz, 2H), 7.86 (s, 1H), 8.02 (dd, J=9.0, 5.4 Hz, 2H); MS (ESI+) m/z 502 (M+H)+, (ESI−) m/z 500 (M−H)−.

1. customThe solvent was removed in vacuo
2. customleaving a cloudy slurry which
3. stirringThe mixture was stirred for 30 minutes at room temperature
4. customThe aqueous layer was removed
5. washthe ethyl acetate layer was washed with 10 mL 10% aqueous NaCl
6. dry with materialdried over anhydrous sodium sulfate (solid)
7. filtrationfiltered
8. customThe solvent was removed in vacuo
9. customleaving a clear yellow oil
10. customPurification on a silica gel column (4 g)
11. washeluting with a gradient of 99.5/0.5 dichloromethane/methanol to 94/6 dichloromethane/methanol over 25 minutes