反应详情

A suspension of (2E)-3-(4-bromo-2-thienyl)acrylic acid (commercially available, 50.2 g, 0.215 mol) in dichloromethane (150 mL) was treated with DMF (2 drops) and SOCl2 (23 mL, 0.315 mol), stirred at room temperature for 48 hours, heated to reflux for 2 hours, and concentrated. The residue was dissolved in dioxane (100 mL) and added to a vigorously stirred solution of NaN3 (25 g, 0.384 mol) in water (100 mL) and dioxane (100 mL) over 10 minutes. The resulting mixture was stirred at room temperature for 2.5 hours and extracted twice with 150 mL of ethyl acetate. The combined organics were washed with water and brine, dried (Na2SO4), filtered, and concentrated. A solution of the residue in dichloromethane (150 mL) was added dropwise over 5 hours to boiling diphenyl ether (150 mL) in a 3-neck flask fitted with 2 air-cooled condensers. The mixture was stirred at reflux for an additional 1 hour, cooled to room temperature, and concentrated. The residue was suspended in diethyl ether (100 mL) and hexanes (200 mL), cooled, and filtered. The filter cake was washed with additional diethyl ether/hexanes and dried to provide 37.4 g of the desired product. MS (ESI(+)) m/e 231 (M+H)+.

1. temperatureheated
2. temperatureto reflux for 2 hours
3. concentrationconcentrated
4. dissolutionThe residue was dissolved in dioxane (100 mL)
5. stirringThe resulting mixture was stirred at room temperature for 2.5 hours
6. extractionextracted twice with 150 mL of ethyl acetate
7. washThe combined organics were washed with water and brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated
11. additionA solution of the residue in dichloromethane (150 mL) was added dropwise over 5 hours
12. customfitted with 2 air-cooled condensers
13. stirringThe mixture was stirred
14. temperatureat reflux for an additional 1 hour
15. temperaturecooled to room temperature
16. concentrationconcentrated
17. temperaturehexanes (200 mL), cooled
18. filtrationfiltered
19. washThe filter cake was washed with additional diethyl ether/hexanes
20. customdried