反应详情

Add ethyl 4-cyano-3-[4-(2-cyanophenyl)phenyl]-5-ethyl-1-methylpyrrole-2-carboxylate to a round bottom flask with a nitrogen inlet, thermocouple and magnetic stirring. Add THF (4.0 volumes). MeOH (1.0 volume) and 1.20 equiv. of 2N LiOH and stir the reaction mixture at RT. After stirring for 24 h no starting material remains. Add Darco (40 w %) and stir the slurry for 30 min. Then filter the reaction mixture through a plug of Hyflo Super Cel® (about ½″ thick) and rinse 2 times with 1 volume of water. Filter this initial filtrate again through a Whatman® GF/F filter to collect small black particulates that escape through the first filtration. Acidify the filtrate slowly with 1 N HCl (1.5 equiv as compared to the LiOH added) {slow addition is very important for polymorph control—about 90 min. addition on 100 g scale}. Stir the milky suspension for 15 min. Filter the thick suspension through a glass frit to obtain a wet solid. Wash this wet solid 4 times with 5 volumes of water (breaking vacuum and stirring the solids with the water each time). Place the wet solid in a vacuum oven at 40° C. overnight (˜15 h) to provide the title compound (92.2% yield).

1. filtrationThen filter the reaction mixture through a plug of Hyflo Super Cel® (about ½″ thick) and
2. washrinse 2 times with 1 volume of water
3. filtrationFilter this initial filtrate again through a Whatman® GF/F
4. filtrationfilter
5. customto collect small black particulates that escape
6. filtrationthrough the first filtration
7. additionadded) {
8. additionslow addition
9. additionis very important for polymorph control—about 90 min. addition on 100 g scale}
10. stirringStir the milky suspension for 15 min
11. filtrationFilter the thick suspension through a glass frit
12. customto obtain a wet solid
13. washWash this wet solid 4 times with 5 volumes of water (
14. stirringstirring the solids with the water each time)
15. customat 40° C.
16. customovernight (˜15 h)