反应详情

温度

25 °C

N-[2-(3-azetidinylamino)-2-oxoethyl]-3-(trifluoromethyl)benzamide (3.44 kg, 4.8 w/w % in 2-MeTHF, 0.548 mol) in 2-methyl tetrahydrofuran (2-MeTHF, 3.3 kg) was added to an inertisized reactor. 4-hydroxy-4-(1,3-thiazol-5-yl)cyclohexanone (108.1 g, 0.537 mol) was added. Pt/C 5% wet (213.8 g) was added. The reactor was rinsed three times with N2, then rinsed three times with H2 and stirred vigorous for 12 hours at 25° C. and 1 bar H2. The catalyst was filtered and the mother liquor cooled to 15° C. 1N HCl (866 ml) was added to the mother liquor. Water (510 ml) was added and the mixture stirred for 30 minutes at 25° C. The layers were allowed to separate during 30 minutes and the organic layer was removed. 607 ml of isopropyl acetate (iPrOAc) was added to the water layer and stirred for 10 minutes. The layers were allowed to separate and the organic layer was removed. iPrOAc (607 ml) was added to the water layer and stirred for 10 minutes; the layers were allowed to separate and the organic layer was removed. 790 ml of iPrOAc was added to the water layer. Then, NaOH 50% (75.10 g) was added. The mixture was heated to 55° C., stirred for 30 minutes at 55° C., cooled to 25° C. over 2 hours and stirred for 3 hours at 25° C. The precipitate was filtered, washed with 152 ml iPrOAc and then washed three times with 152 ml water. The precipitate was dried for 20 hours at 40° C. under vacuum and N2 atmosphere to afford the title compound.

1. washThe reactor was rinsed three times with N2
2. washrinsed three times with H2
3. filtrationThe catalyst was filtered
4. temperaturethe mother liquor cooled to 15° C
5. addition1N HCl (866 ml) was added to the mother liquor
6. additionWater (510 ml) was added
7. stirringthe mixture stirred for 30 minutes at 25° C
8. customto separate during 30 minutes
9. customthe organic layer was removed
10. addition607 ml of isopropyl acetate (iPrOAc) was added to the water layer
11. stirringstirred for 10 minutes
12. customto separate
13. customthe organic layer was removed
14. additioniPrOAc (607 ml) was added to the water layer
15. stirringstirred for 10 minutes
16. customto separate
17. customthe organic layer was removed
18. addition790 ml of iPrOAc was added to the water layer
19. additionThen, NaOH 50% (75.10 g) was added
20. temperatureThe mixture was heated to 55° C.
21. stirringstirred for 30 minutes at 55° C.
22. temperaturecooled to 25° C. over 2 hours
23. stirringstirred for 3 hours at 25° C
24. filtrationThe precipitate was filtered
25. washwashed with 152 ml iPrOAc
26. washwashed three times with 152 ml water
27. dry with materialThe precipitate was dried for 20 hours at 40° C. under vacuum and N2 atmosphere