Реакция #45394

Уравнение реакции

NaN3

dioxane

(2E)-3-(4-bromo-2-thienyl)acrylic acid

SOCl2

→

desired product

3-bromothieno[3,2-c]pyridin-4(5H)-one

Растворители

water

dichloromethane

Условия реакции

Обработка

1. 1
   Температураheated
2. 2
   Температураto reflux for 2 hours
3. 3
   Концентрированиеconcentrated
4. 4
   workup.DISSOLUTIONThe residue was dissolved in dioxane (100 mL)
5. 5
   workup.STIRRINGThe resulting mixture was stirred at room temperature for 2.5 hours
6. 6
   Экстракцияextracted twice with 150 mL of ethyl acetate
7. 7
   ПромывкаThe combined organics were washed with water and brine
8. 8
   Сушкаdried (Na2SO4)
9. 9
   Фильтрацияfiltered
10. 10
    Концентрированиеconcentrated
11. 11
    workup.ADDITIONA solution of the residue in dichloromethane (150 mL) was added dropwise over 5 hours
12. 12
    Другоеfitted with 2 air-cooled condensers
13. 13
    workup.STIRRINGThe mixture was stirred
14. 14
    Температураat reflux for an additional 1 hour
15. 15
    Температураcooled to room temperature
16. 16
    Концентрированиеconcentrated
17. 17
    Температураhexanes (200 mL), cooled
18. 18
    Фильтрацияfiltered
19. 19
    ПромывкаThe filter cake was washed with additional diethyl ether/hexanes
20. 20
    Другоеdried

Методика

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)+.

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