Potassium Carbonate → (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyano-3-fluorophenoxy)-2-hydroxy-2-methylpropanamide

HRID 83111

Reaktionsgleichung

Reaktionsgleichung von HRID 83111
Br[NH-].Br[CH2:4][C@@:5]([OH:22])([CH3:21])[C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[C:11]([C:17]([F:20])([F:19])[F:18])[CH:10]=1)=[O:7].C([O-])([O-])=O.[K+].[K+].[F:29][C:30]1[CH:37]=[C:36]([OH:38])[CH:35]=[CH:34][C:31]=1[C:32]#[N:33]>CC(C)=O.CC(O)C.O>[C:15]([C:12]1[CH:13]=[CH:14][C:9]([NH:8][C:6](=[O:7])[C@:5]([OH:22])([CH3:21])[CH2:4][O:38][C:36]2[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[C:30]([F:29])[CH:37]=2)=[CH:10][C:11]=1[C:17]([F:20])([F:19])[F:18])#[N:16]

Komponenten

8

Edukt 4

HCID 11430Potassium Carbonate2×HCID 27346752-Fluoro-4-hydroxybenzonitrileHCID 10450565(2R)-3-bromo-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamideHCID 86618840Bromoamide

Produkt 1

HCID 16045149(S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyano-3-fluorophenoxy)-2-hydroxy-2-methylpropanamideAusbeute 23 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 180AcetoneLösungsmittelHCID 962WaterLösungsmittelHCID 3776IsopropanolLösungsmittel

Versuchsvorschrift

A mixture of bromoamide ((2R)-3-bromo-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide, R-19 (2.0 g, 5.70 mmol), anhydrous K2CO3 (2.4 g, 17.1 mmol) in 50 mL of acetone was heated to reflux for 2 h and then concentrated under reduced pressure to give a solid. The resulting solid was treated with 2-fluoro-4-hydroxybenzonitrile (1.2 g, 8.5 mmol) and anhydrous K2CO3 (1.6 g, 11.4 mmol) in 50 mL of 2-propanol was heated to reflux for 3 h and then concentrated under reduced pressure to give a solid. The residue was treated with 100 mL of H2O and then extracted with EtOAc (2×100 mL). The combined EtOAc extracts were washed with 10% NaOH (4×100 mL) and brine, successively. The organic layer was dried over MgSO4 and then concentrated under reduced pressure to give an oil which was crystallized from CH2Cl2/hexane to give 0.5 g (23%) of (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyano-3-fluorophenoxy)-2-hydroxy-2-methylpropanamide as a colorless solid.

Aufarbeitung

  1. temperatureto reflux for 2 h
  2. concentrationconcentrated under reduced pressure
  3. customto give a solid
  4. temperaturewas heated
  5. temperatureto reflux for 3 h
  6. concentrationconcentrated under reduced pressure
  7. customto give a solid
  8. extractionextracted with EtOAc (2×100 mL)
  9. washThe combined EtOAc extracts were washed with 10% NaOH (4×100 mL) and brine
  10. dry with materialThe organic layer was dried over MgSO4
  11. concentrationconcentrated under reduced pressure
  12. customto give an oil which
  13. customwas crystallized from CH2Cl2/hexane

Quellen und Nachweise

ORD-Eintrag
ord-ef695c18e176493685816d0364a10b3f
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846756B2

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