反应详情

温度

-8 °C

The nitro compound 8 (47.87 g, 0.223 mol) was dissolved in acetonitrile (240 ml) and cooled to −8° C. Triethylamine (33.8 g, 0.334 mol) was added. A clear dark solution was formed. Triflic anhydride (69.17 g, 0.245 mol) was added slowly and the reaction temperature was maintained at −10° C. 10 minutes after addition was complete, TLC analysis indicate the completion of triflate formation. Cooling bath was removed. Alkyne 5 (47.46 g, 0.234 mol) was added. The solution was degassed 3 times by evacuating the flask and backfilling it with nitrogen. The solution was then transferred into an addition funnel. Into a separate reaction flask was added acetonitrile (240 ml) and triethylamine (22.5 g, 0.223 mol). The solution was degassed 3 times by exposing the reaction flask to vacuum and nitrogen alternatively. Dichlorobis(triphenylphosphine) palladium (II) (3.13 g, 0.0045 mol) was added to the solution and the solution was degassed again 3 times. This solution was heated to 65° C. under protection of nitrogen. Once the temperature reached 65° C., one quarter of the solution of alkyne 5 and triflate in addition funnel was quickly added to the reaction flask. The remaining solution in addition funnel was added over 30 minutes at 65° C. After the addition was complete, the reaction solution was stirred at 65° C. for 2 hours. HPLC analysis indicated the reaction was complete. Reaction mixture was cooled to room temperature. Solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (500 ml) and washed with water (300 ml). The aqueous phase was separated and back extracted with ethyl acetate (200 ml). The combined organic solution was washed with water (200 ml). It was then concentrated to dryness to provide a dark oil residue (140 g). This crude product was used in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 2.87 (d, br, 3H), 3.755 (s, 3H), 4.011 (s, 3H), 4.50 (s, br, 2H), 7.21 (s, br, 2H), 7.55 (d, 2H, J=9 Hz), 7.80 (dd, 1H, J=2.7 Hz and J=7.2 Hz), 7.86 (dd, 1H, J=2.7 Hz and J=8.1 Hz).

1. customA clear dark solution was formed
2. temperaturethe reaction temperature was maintained at −10° C
3. addition10 minutes after addition
4. temperatureCooling bath
5. customwas removed
6. customThe solution was degassed 3 times
7. customby evacuating the flask
8. customThe solution was then transferred into an addition funnel
9. customInto a separate reaction flask
10. customThe solution was degassed 3 times
11. customthe solution was degassed again 3 times
12. temperatureThis solution was heated to 65° C. under protection of nitrogen
13. customreached 65° C.
14. additionone quarter of the solution of alkyne 5 and triflate in addition funnel
15. additionwas quickly added to the reaction flask
16. additionThe remaining solution in addition funnel
17. additionwas added over 30 minutes at 65° C
18. additionAfter the addition
19. customReaction mixture
20. temperaturewas cooled to room temperature
21. customSolvent was removed under reduced pressure
22. dissolutionThe residue was dissolved in ethyl acetate (500 ml)
23. washwashed with water (300 ml)
24. customThe aqueous phase was separated
25. extractionback extracted with ethyl acetate (200 ml)
26. washThe combined organic solution was washed with water (200 ml)
27. concentrationIt was then concentrated to dryness