反应详情

温度

25 °C

Ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate (8.0 Kg), acetone (80 L), lithium hydroxide monohydrate (1.2 Kg), and water (12 L) were mixed and heated to reflux. The mixture was maintained under reflux until reaction completion. After the reaction was complete, the mass was cooled to about 25° C., ethyl acetate (120 L) was added, and pH was adjusted to about 1 to 2 with hydrochloric acid (3.2 L). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (80 L). The combined organic material was washed with water (3×80 L), and treated with activated carbon at about 50° C. The combined organic material was filtered, and the filtrate was evaporated completely under vacuum below 45° C. Acetonitrile (16 L) was added to the residue and the solvent was distilled. Acetonitrile (80 L) was added to the residue and the mixture was heated to about 65° C. and maintained for about 1 hour. The mass was cooled to about 30° C. and maintained for about 1 hour. The formed solid was filtered and washed with acetonitrile (32 L). The wet solid was dried at about 60° C. to a constant weight to yield 5.2 Kg of the title compound. Purity by HPLC: 99.9%.

1. temperatureheated to reflux
2. temperatureThe mixture was maintained
3. temperatureunder reflux until reaction completion
4. customThe organic layer was separated
5. extractionthe aqueous layer was extracted with ethyl acetate (80 L)
6. washThe combined organic material was washed with water (3×80 L)
7. additiontreated with activated carbon at about 50° C
8. filtrationThe combined organic material was filtered
9. customthe filtrate was evaporated completely under vacuum below 45° C
10. additionAcetonitrile (16 L) was added to the residue
11. distillationthe solvent was distilled
12. additionAcetonitrile (80 L) was added to the residue
13. temperaturethe mixture was heated to about 65° C.
14. temperaturemaintained for about 1 hour
15. temperatureThe mass was cooled to about 30° C.
16. temperaturemaintained for about 1 hour
17. filtrationThe formed solid was filtered
18. washwashed with acetonitrile (32 L)
19. customThe wet solid was dried at about 60° C. to a constant weight