Methane → 4-Cyano-3-[4-(2-cyanophenyl)phenyl]-5-ethyl-1-methylpyrrole-2-carboxylic acid

HRID 1865125Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1865125
[C:1]([C:3]1[C:4]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:28]#[N:29])=[CH:18][CH:17]=2)=[C:5]([C:11]([O:13]CC)=[O:12])[N:6]([CH3:10])[C:7]=1[CH2:8][CH3:9])#[N:2].C1COCC1.[Li+].[OH-].C>CO>[C:1]([C:3]1[C:4]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:28]#[N:29])=[CH:18][CH:17]=2)=[C:5]([C:11]([OH:13])=[O:12])[N:6]([CH3:10])[C:7]=1[CH2:8][CH3:9])#[N:2]

Komponenten

6

Edukt 4

HCID 297MethaneHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 69020544Ethyl 4-cyano-3-[4-(2-cyanophenyl)phenyl]-5-ethyl-1-methylpyrrole-2-carboxylate

Produkt 1

HCID 112912124-Cyano-3-[4-(2-cyanophenyl)phenyl]-5-ethyl-1-methylpyrrole-2-carboxylic acidAusbeute 92,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-90c44ba633cb48b6b6220018e5ea1457
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07625932B2

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