반응 #2467996

반응 방정식

diisopropylamine

7-Chloro-2-ethoxy-benzo[d][1,3]oxazin-4-one

butyl lithium

thiophen-3-carboxylic acid

→

title compound

7-Chloro-9H-3-thia-9-aza-benzo[f]azulene-4,10-dione

용매

water

tetrahydrofuran

hexane

tetrahydrofuran

반응 조건

후처리

1. 1
   기타A 4-necked, round-bottomed flask, equipped with a mechanical stirrer
2. 2
   workup.ADDITIONdigital thermometer, addition funnel and a condenser with nitrogen inlet-outlet
3. 3
   온도while maintaining the internal temperature at 0° C
4. 4
   workup.STIRRINGThe mixture is stirred for an additional hour
5. 5
   온도before being cooled to −65° C
6. 6
   workup.ADDITIONis added over 1 hour
7. 7
   workup.STIRRINGThe mixture is stirred at −65° C. for 1 hour
8. 8
   온도warmed to 0° C. over 40 min
9. 9
   workup.STIRRINGstirred for 30 min
10. 10
    온도be raised to 20° C
11. 11
    workup.STIRRINGThe mixture is stirred at this temperature for 16 hours
12. 12
    농축before being concentrated under reduced pressure
13. 13
    기타to remove the organic solvents
14. 14
    workup.ADDITIONTo the residue ethanol (11 L) and lithium hydroxide (295.5 g) are added
15. 15
    온도The mixture is heated to 60° C. over 45 min
16. 16
    workup.STIRRINGstirred at this temperature for 3 hours
17. 17
    온도the temperature is raised to 75° C. over 10 min
18. 18
    workup.ADDITIONhydrochloric acid (2 L, 37% m/m) is added over 10 min under gentle reflux
19. 19
    workup.STIRRINGThe mixture is stirred for an hour at 60-65° C
20. 20
    온도The suspension is then cooled to room temperature
21. 21
    기타the solid is collected
22. 22
    세척washed 5 times with water (4.2 L total), ethanol (5 L total)
23. 23
    기타dried under vacuum (60° C., 50 mbar)

실험 절차

A 4-necked, round-bottomed flask, equipped with a mechanical stirrer, digital thermometer, addition funnel and a condenser with nitrogen inlet-outlet is charged with thiophen-3-carboxylic acid (448.2 g) and tetrahydrofuran (4.7 L) and stirred to dissolution. The solution is cooled to 0° C. and diisopropylamine (245 mL) is added over 5 min. Then, a 1.6M solution of butyl lithium in hexane (4.8 L) is added over 2.5 hours while maintaining the internal temperature at 0° C. The mixture is stirred for an additional hour before being cooled to −65° C. Then 7-Chloro-2-ethoxy-benzo[d][1,3]oxazin-4-one (830 g), dissolved in tetrahydrofuran (1.7 L) is added over 1 hour. The mixture is stirred at −65° C. for 1 hour, then warmed to 0° C. over 40 min and stirred for 30 min. Then water (4 L) is added over 10 min letting the temperature be raised to 20° C. The mixture is stirred at this temperature for 16 hours before being concentrated under reduced pressure to remove the organic solvents. To the residue ethanol (11 L) and lithium hydroxide (295.5 g) are added. The mixture is heated to 60° C. over 45 min, stirred at this temperature for 3 hours, then the temperature is raised to 75° C. over 10 min and hydrochloric acid (2 L, 37% m/m) is added over 10 min under gentle reflux. The mixture is stirred for an hour at 60-65° C. The suspension is then cooled to room temperature and the solid is collected, washed 5 times with water (4.2 L total), ethanol (5 L total) and dried under vacuum (60° C., 50 mbar) to yield the title compound with a melting point of >280° C.

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