反应详情

To a mixture of #13 (5.65 g, 20.2 mmol, 1 eq.) in acetone (101 mL, 0.2 M) was added bromoacetaldehyde diethyl acetal (8.76 mL, 58.2 mmol, 2.89 eq.) and 2 drops of 4 M hydrochloric acid in dioxane. The mixture was degassed with nitrogen three times before being heated to reflux. After 2 hours, the reaction was cooled to room temperature and concentrated in vacuo. The residue was dissolved in ethyl acetate, washed with saturated aqueous sodium bicarbonate solution and washed with brine. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting crude orange oil was diluted with ethyl acetate before being concentrated in vacuo onto silica and purified by silica gel chromatography (Gradient: 0% to 35% ethyl acetate in heptane) and then by reverse phase chromatography (Method A) to give #14 (625 mg, 10%); HPLC (Protocol E): m/z 304.5 [M+H+], 248.9 [(M−2-methylprop-1-ene)+H+], retention time=7.416 minutes; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, major rotamer: δ 7.75 (d, J=3.3 Hz, 1H), 7.75 (br d, J=8.6 Hz, 1H), 7.61 (br d, J=3.1 Hz, 1H), 7.25-7.30 (m, 5H), 4.99 (ddd, J=10.5, 8.9, 4.5 Hz, 1H), 3.29-3.36 (m, 1H, assumed; partially obscured by water signal), 2.98 (dd, J=13.8, 10.6 Hz, 1H), 1.31 (s, 9H).

1. customThe mixture was degassed with nitrogen three times
2. temperaturebefore being heated to reflux
3. concentrationconcentrated in vacuo
4. dissolutionThe residue was dissolved in ethyl acetate
5. washwashed with saturated aqueous sodium bicarbonate solution
6. washwashed with brine
7. dry with materialThe organic layer was dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. additionThe resulting crude orange oil was diluted with ethyl acetate
11. concentrationbefore being concentrated in vacuo onto silica
12. custompurified by silica gel chromatography (Gradient: 0% to 35% ethyl acetate in heptane)