反应详情

(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamido)-2-methylpropanoic acid: A 25 mL round bottomed flask equipped with a magnetic stir bar and reflux condenser was charged with (E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid (400 mg, 0.82 mmol) and 1,2-dichloroethane (DCE) (5 mL). Thionyl chloride (0.12 mL, 1.64 mmol) was added neat in one portion and the resulting reaction mixture was heated at reflux for 2 h. After which time, reaction mixture was allowed to cool and concentrated to give the crude acid chloride which was used without further purification. To a solution containing NaHCO3 (68.8 mg, 0.82 mmol), 2-amino-2-methylpropanoic acid (84 mg, 0.82 mmol) and dodecyltrimethylammonium bromide (2.52 mg, 8.19 μmol) in 10 mL of THF was added to the acid chloride in THF (1 mL). The resulting mixture was heated at reflux for 18 h. Reaction mixture was allowed to cool and added to water, made acidic with 0.1N HCl, extracted (3×) with Et2O, washed (1×) with brine, dried over MgSO4, filtered and evaporated to afford the title compound as a light brown foam (400 mg, 85%): 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J=1.6 Hz, 1H), 7.59 (d, J=8.0 Hz, 1H), 7.40 (s, 2H), 7.37 (dd, J=8.1, 1.6 Hz, 1H), 6.63 (s, 1H), 6.53 (d, J=15.9 Hz, 1H), 6.38 (dd, J=15.9, 7.9 Hz, 1H), 4.10 (p, J=8.3 Hz, 1H), 1.73 (s, 6H). This material is used without further purification.

1. temperaturereflux condenser
2. customthe resulting reaction mixture
3. temperaturewas heated
4. temperatureat reflux for 2 h
5. customAfter which time, reaction mixture
6. temperatureto cool
7. concentrationconcentrated
8. customto give the crude acid chloride which
9. customwas used without further purification
10. temperatureThe resulting mixture was heated
11. temperatureat reflux for 18 h
12. customReaction mixture
13. temperatureto cool
14. extractionextracted (3×) with Et2O
15. washwashed (1×) with brine
16. dry with materialdried over MgSO4
17. filtrationfiltered
18. customevaporated