反应详情

Add isopropyl magnesium chloride (2M solution in tetrahydrofuran, 0.496 ml, 0.992 mmol) to a solution of 1-(4-iodo-benzyloxy)-2-propyl-3-trimethylsilanyloxy-4-(1-trimethylsilanyloxy-vinyl)-benzene (500 mg, 0.901 mmol) in tetrahydrofuran (0.1M) at 0° C. After 15 minutes, warm to room temperature. After 1 hour, cool to −78° C. Add sodium hydride (60% dispersion, 24 mg, 0.992 mmol) to a solution of 3-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-benzaldehyde (189 mg, 0.992 mmol) in tetrahydrofuran (0.1M). Sonicate the solution for 5 minutes, then add it via syringe to the gringard reagent. After 30 minutes warm the reaction to room temperature. Quench with 10% aq hydrochloric acid (3 mL). Pour the reaction into brine and extract with 25% isopropyl alcohol:75% dichloromethane. Combine organic layers, dry with sodium sulfate, filter and concentrate under reduced pressure to give a residue. Purify the residue by flash chromatography eluting with ethyl acetate:hexanes:acetic acid 50%:50%:0.1% to yield the title product as a off white solid (110 mg, 26%): 1H NMR (DMSO-d6) δ 0.86 (t, 3H), 1.47 (sextet, 2H), 2.56 (m, 5H), 5.21 (s, 2H), 5.79 (d, 1H), 6.11 (d, 1H), 6.70 (d, 1H), 7.41 (q, 4H), 7.51 (t, 1H), 7.63 (t, 2H), 7.78 (d, 1H), 7.90 (s, 1H), 12.83 (s, 1H), 12.97 (bs, 1H); MS (esi negative) m/z (rel intensity) 473 (100).

1. waitAfter 1 hour
2. temperaturecool to −78° C
3. customSonicate the solution for 5 minutes
4. additionadd it via syringe to the gringard reagent
5. temperatureAfter 30 minutes warm
6. customthe reaction to room temperature
7. customQuench with 10% aq hydrochloric acid (3 mL)
8. additionPour
9. customthe reaction into brine
10. extractionextract with 25% isopropyl alcohol
11. dry with materialCombine organic layers, dry with sodium sulfate
12. filtrationfilter
13. concentrationconcentrate under reduced pressure
14. customto give a residue
15. customPurify the residue by flash chromatography
16. washeluting with ethyl acetate