Reacción #2467996

Ecuación de reacción

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

Disolventes

water

tetrahydrofuran

hexane

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroA 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
   Temperaturawhile maintaining the internal temperature at 0° C
4. 4
   workup.STIRRINGThe mixture is stirred for an additional hour
5. 5
   Temperaturabefore 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
   Temperaturawarmed to 0° C. over 40 min
9. 9
   workup.STIRRINGstirred for 30 min
10. 10
    Temperaturabe raised to 20° C
11. 11
    workup.STIRRINGThe mixture is stirred at this temperature for 16 hours
12. 12
    Concentraciónbefore being concentrated under reduced pressure
13. 13
    Otroto remove the organic solvents
14. 14
    workup.ADDITIONTo the residue ethanol (11 L) and lithium hydroxide (295.5 g) are added
15. 15
    TemperaturaThe mixture is heated to 60° C. over 45 min
16. 16
    workup.STIRRINGstirred at this temperature for 3 hours
17. 17
    Temperaturathe 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
    TemperaturaThe suspension is then cooled to room temperature
21. 21
    Otrothe solid is collected
22. 22
    Lavadowashed 5 times with water (4.2 L total), ethanol (5 L total)
23. 23
    Otrodried under vacuum (60° C., 50 mbar)

Procedimiento

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.

Fuente