반응 #2467998

반응 방정식

hexachloroethane

[7-Chloro-10-methoxy-3-thia-9-aza-benzo[f]azulen-(4Z)-ylidene]-acetic acid

n-butyl lithium

diisopropylamine

→

[2,7-Dichloro-10-methoxy-3-thia-9-aza-benzo[f]azulen-(4Z)-ylidene]-acetic acid

용매

tetrahydrofuran

tetrahydrofuran

water

tetrahydrofuran

반응 조건

후처리

1. 1
   기타A round-bottomed flask, equipped with a magnetic stirrer
2. 2
   workup.ADDITIONdigital thermometer, addition funnel and a condenser with nitrogen inlet-outlet
3. 3
   workup.ADDITIONAfter addition the reaction mixture
4. 4
   workup.ADDITIONis added dropwise over 1 hour
5. 5
   온도while maintaining the temperature at −70° C
6. 6
   workup.STIRRINGStirring
7. 7
   온도is maintained for 1 hour at −78° C
8. 8
   온도while maintaining the temperature at −25° C
9. 9
   온도to slowly warm up to 0° C. over 30 min
10. 10
    workup.WAITkept at this temperature for 30 min
11. 11
    농축the resulting emulsion concentrated under vacuum
12. 12
    기타to remove the solvent
13. 13
    workup.ADDITIONThen tert-butylmethylether (5.25 L) and water (3 L) are added
14. 14
    workup.STIRRINGAfter vigorous stirring the organic phase
15. 15
    기타is removed
16. 16
    기타to get a pH value of 2-3
17. 17
    기타Afterwards, the organic phase is separated
18. 18
    농축concentrated to 1/10, methanol (6.2 L)
19. 19
    workup.ADDITIONis added
20. 20
    온도the temperature raised to 65° C. over 40 min
21. 21
    workup.DISTILLATIONThe solution is distilled to a volume of 3.4 L
22. 22
    온도the resulting suspension cooled to −15° C.
23. 23
    workup.STIRRINGstirred for 1 hour
24. 24
    기타The crystalline precipitation
25. 25
    여과is collected by filtration
26. 26
    세척washed with cold methanol (500 mL)
27. 27
    기타dried under vacuum (50° C., 20-50 mmbar)

실험 절차

A round-bottomed flask, equipped with a magnetic stirrer, digital thermometer, addition funnel and a condenser with nitrogen inlet-outlet, is charged with diisopropylamine (462.9 mL) and tetrahydrofuran (4.2 L). The solution is cooled to −78° C. and n-butyl lithium (1.71 L, 1.6 M in hexane) is added over a period of 1 hour. After addition the reaction mixture is stirred for 1 hour and [7-Chloro-10-methoxy-3-thia-9-aza-benzo[f]azulen-(4Z)-ylidene]-acetic acid (350 g), dissolved in tetrahydrofuran (1.4 L), is added dropwise over 1 hour while maintaining the temperature at −70° C. Stirring is maintained for 1 hour at −78° C. Afterwards the yellow solution is transferred through a cold tube to a solution of hexachloroethane (779 g), dissolved in tetrahydrofuran (4.2 L), over a period of 45 min while maintaining the temperature at −25° C. The yellow solution is then allowed to slowly warm up to 0° C. over 30 min and kept at this temperature for 30 min. Then, deionized water (2.26 kg) is added over 5 min and the resulting emulsion concentrated under vacuum to remove the solvent. Then tert-butylmethylether (5.25 L) and water (3 L) are added. After vigorous stirring the organic phase is removed and replaced with isopropyl acetate (7 L). Then the mixture is acidified with phosphoric acid (339 L) to get a pH value of 2-3. Afterwards, the organic phase is separated and concentrated to 1/10, methanol (6.2 L) is added and the temperature raised to 65° C. over 40 min. The solution is distilled to a volume of 3.4 L, the resulting suspension cooled to −15° C. and stirred for 1 hour. The crystalline precipitation is collected by filtration, washed with cold methanol (500 mL) and dried under vacuum (50° C., 20-50 mmbar) to yield [2,7-Dichloro-10-methoxy-3-thia-9-aza-benzo[f]azulen-(4Z)-ylidene]-acetic acid with a melting point of 195-197° C.

출처