Acetic Acid → 4-(2,6-Difluorophenyl)-2,2-dimethyl-5-oxopiperazine-1-carboxylic acid t-butyl ester

HRID 1694927Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1694927
CC(C)([O-])C.[K+].[C:7]([O:11][C:12](=[O:31])[NH:13][C:14]([CH3:30])([CH3:29])[CH2:15][N:16]([C:25](=[O:28])[CH2:26]Br)[C:17]1[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=1[F:24])([CH3:10])([CH3:9])[CH3:8].C(O)(=O)C>O1CCCC1>[C:7]([O:11][C:12]([N:13]1[CH2:26][C:25](=[O:28])[N:16]([C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])[CH2:15][C:14]1([CH3:30])[CH3:29])=[O:31])([CH3:10])([CH3:9])[CH3:8]

Komponenten

5

Edukt 3

HCID 176Acetic AcidHCID 23665647Potassium tert-butoxideHCID 66645630{2-[(2-Bromoacetyl)-(2,6-difluorophenyl)amino]-1,1-dimethylethyl}carbamic acid t-butyl ester

Produkt 1

HCID 666456784-(2,6-Difluorophenyl)-2,2-dimethyl-5-oxopiperazine-1-carboxylic acid t-butyl esterAusbeute 83 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

A solution of 2.05 g of potassium t-butoxide (18.3 mmol) in tetrahydrofuran (120 ml) was added to a solution of 5.14 g of {2-[(2-bromoacetyl)-(2,6-difluorophenyl)amino]-1,1-dimethylethyl}carbamic acid t-butyl ester obtained in Example (60b) (12.2 mmol) in tetrahydrofuran (120 ml) under a nitrogen atmosphere and under cooling in a dry ice-acetone bath over 30 minutes, and the mixture was stirred at the same temperature for 30 minutes. 0.33 ml of acetic acid (6.10 mmol) was added to the reaction mixture. After returning to room temperature, the solvent was evaporated under reduced pressure. The residue was diluted with water, followed by extraction with ethyl acetate. Then, the organic layer was washed with brine and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:hexane/ethyl acetate=3/1) to obtain 3.43 g of the title compound (yield: 83%).

Aufarbeitung

  1. temperatureunder cooling in a dry ice-acetone bath over 30 minutes
  2. customAfter returning to room temperature
  3. customthe solvent was evaporated under reduced pressure
  4. additionThe residue was diluted with water
  5. extractionfollowed by extraction with ethyl acetate
  6. washThen, the organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationAfter filtration
  9. customthe solvent was evaporated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (elution solvent:hexane/ethyl acetate=3/1)

Quellen und Nachweise

ORD-Eintrag
ord-31a4beba274545a290523db3e813ff96
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08158790B2

Notizen zur Reaktion

Wird geladen…