反应详情

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 251d (1.10 g, 2.95 mmol), 37% solution of formaldehyde in water (111 mg, 3.70 mmol) and methanol (15 mL). A suspension of sodium cyanoborohydride (540 mg, 8.60 mmol) and zinc chloride (600 mg, 4.40 mmol) in methanol (10 mL) was added, and the reaction was stirred at room temperature for 4 h. After this time, the reaction mixture was concentrated, and the residue was partitioned between 90:10 methylene chloride/methanol (250 mL) and 10% aqueous potassium carbonate (100 mL). The aqueous layer was extracted with 90:10 methylene chloride/methanol (3×150 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica, 0% to 50% methanol/methylene chloride) to afford a 80% yield (830 mg) of 251e as an brown solid: mp 100-101° C.; 1H NMR (500 MHz, DMSO-d6) d 8.66 (s, 1H), 8.55 (d, 1H, J=2.5 Hz), 7.86 (d, 1H, J=3.0 Hz), 7.47 (d, 1 h, J=2.5 Hz), 7.31 (d, 1H, J=9.0 Hz), 7.24 (dd, 1H, J=9.5, 3.5 Hz), 4.76 (m, 1H), 3.77 (t, 2H, J=7.5 Hz), 3.50 (s, 3H), 3.03 (t, 2H, J=7.5 Hz), 2.26 (s, 3H); MS (ESI+) m/z 366.0 (M+H).

1. customA 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer
2. customwas purged with nitrogen
3. additionwas added
4. concentrationAfter this time, the reaction mixture was concentrated
5. customthe residue was partitioned between 90:10 methylene chloride/methanol (250 mL) and 10% aqueous potassium carbonate (100 mL)
6. extractionThe aqueous layer was extracted with 90:10 methylene chloride/methanol (3×150 mL)
7. dry with materialThe combined organic extracts were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe resulting residue was purified by column chromatography (silica, 0% to 50% methanol/methylene chloride)