Reaktion #6314

Reaktionsgleichung

4,5-dihydro-7-[3-(trifluoromethyl)-phenyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide

potassium tert-butoxide

carbon disulfide

→

desired product

Ausbeute 90.5%

5-(Methylthio)-8-[3-(trifluoromethyl)phenyl]-3H,6H-1,4,5a,8a-tetraazaacenaphthylen-3-one

Ausbeute 90.5%

Lösungsmittel

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONis added portionwise over 25 minutes
2. 2
   Temperaturwhile maintaining a temperature less than 4° C
3. 3
   Temperaturwhile maintaining the temperature below 2° C
4. 4
   WaschenThe funnel is rinsed with 500 ml of tetrahydrofuran
5. 5
   workup.STIRRINGto stir for 45 minutes
6. 6
   TemperaturWhile maintaining the temperature from -8° C. to 3.2° C.
7. 7
   workup.ADDITION1870 g of methyl iodide is added dropwise through a dropping funnel
8. 8
   WaschenThe funnel is rinsed with 500 ml of tetrahydrofuran
9. 9
   workup.STIRRINGto stir for 1 hour
10. 10
    workup.ADDITIONAn additional 3804 g of methyl iodide is added
11. 11
    workup.STIRRINGThe reaction mixture is stirred for 50 minutes
12. 12
    Temperaturwhile cooling to -23.1° C
13. 13
    workup.ADDITIONAn additional 2530 g of potassium tert-butoxide is added over 2 hours
14. 14
    Temperaturwhile maintaining a temperature of -23.1° C. to 10.0° C
15. 15
    workup.ADDITIONAfter half of the potassium tert-butoxide is added another 300 ml of methyl iodide
16. 16
    workup.ADDITIONis added
17. 17
    workup.ADDITIONThe remaining potassium tert-butoxide is added
18. 18
    workup.STIRRINGthe reaction mixture stirred
19. 19
    Temperaturwhile warming to room temperature overnight
20. 20
    workup.ADDITIONThe reaction mixture is diluted with 3 kg of ice and 10 L of water
21. 21
    workup.ADDITIONthen added to 80 L of water
22. 22
    workup.STIRRINGwith stirring
23. 23
    WaschenThe reaction flask is rinsed with 26 L of water which
24. 24
    workup.ADDITIONis added to the ice and water containing the original reaction mixture
25. 25
    workup.STIRRINGStirring
26. 26
    workup.WAITis continued for 40 minutes
27. 27
    Filtrationthe solids collected by filtration
28. 28
    WaschenThe filter cake is washed with 20 L of water
29. 29
    Sonstigedried at 30 mm Hg, 35° C.

Vorschrift

A solution of 3.18 kg of 4,5-dihydro-7-[3-(trifluoromethyl)-phenyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide in 30 L of tetrahydrofuran is cooled to 2.8° C. under nitrogen and stirred while 1370 g of potassium tert-butoxide is added portionwise over 25 minutes while maintaining a temperature less than 4° C. The reaction mixture is stirred at -6.2° C. for 45 minutes. To the reaction mixture is added 850 g of carbon disulfide through a dropping funnel over a 10 minute period while maintaining the temperature below 2° C. The funnel is rinsed with 500 ml of tetrahydrofuran and the reaction mixture allowed to stir for 45 minutes. While maintaining the temperature from -8° C. to 3.2° C.. 1870 g of methyl iodide is added dropwise through a dropping funnel. The funnel is rinsed with 500 ml of tetrahydrofuran and the reaction mixture allowed to stir for 1 hour. An additional 3804 g of methyl iodide is added. The reaction mixture is stirred for 50 minutes while cooling to -23.1° C. An additional 2530 g of potassium tert-butoxide is added over 2 hours while maintaining a temperature of -23.1° C. to 10.0° C. After half of the potassium tert-butoxide is added another 300 ml of methyl iodide is added. The remaining potassium tert-butoxide is added and the reaction mixture stirred while warming to room temperature overnight. The reaction mixture is diluted with 3 kg of ice and 10 L of water then added to 80 L of water with stirring. The reaction flask is rinsed with 26 L of water which is added to the ice and water containing the original reaction mixture. Stirring is continued for 40 minutes and the solids collected by filtration. The filter cake is washed with 20 L of water and dried at 30 mm Hg, 35° C. to afford 3.4 kg (90%) of the desired product.

Quelle