Lithium Hexamethyldisilazide → (1S,5S)-7-Hydroxy-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl ester

HRID 1917343Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1917343
[C:1]([O:5][C:6]([C:8]1([CH2:22][CH:23]2[CH2:25][O:24]2)[CH2:12][C:11](=[O:13])[N:10]([C@@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si](C)(C)[N-][Si](C)(C)C.[Li+]>O1CCCC1>[C:1]([O:5][C:6]([C@@:8]12[CH2:22][CH:23]([OH:24])[CH2:25][C@@H:12]1[C:11](=[O:13])[N:10]([C@@H:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15])[CH2:9]2)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Komponenten

4

Edukt 2

HCID 2733832Lithium HexamethyldisilazideHCID 86664649HCID 86664649, Verbindung

Produkt 1

HCID 67491063(1S,5S)-7-Hydroxy-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl esterAusbeute 26 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

3-(Oxiran-2-ylmethyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (4.2 g, 12.16 mmol) was dissolved in tetrahydrofuran (50 mL). A 1 M solution of lithium hexamethyldisilazide in tetrahydrofuran (18 mL, 1.5 equivalents) was added in an argon atmosphere at −78° C., and the mixture was gradually heated. When the reaction temperature reached about room temperature, the reaction was quenched with an ammonium chloride solution, followed by extraction with ethyl acetate. The extract was dried over magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=4:1→2:1→1:1→1:2) to give 1.07 g (26%) of the title compound having a single isomer as a colorless oil. 1.0 g (24%) of the raw material was collected. 1.20 g (29%) of a four-membered ring-closed compound as a by-product was obtained as a diastereomer mixture.

Aufarbeitung

  1. temperaturethe mixture was gradually heated
  2. customreached about room temperature
  3. customthe reaction was quenched with an ammonium chloride solution
  4. extractionfollowed by extraction with ethyl acetate
  5. dry with materialThe extract was dried over magnesium sulfate
  6. filtrationAfter filtration
  7. customthe solvent was evaporated under reduced pressure
  8. customThe resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=4:1→2:1→1:1→1:2)

Quellen und Nachweise

ORD-Eintrag
ord-81ca90c1e9cc449a97ce6729d18a0618
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08618094B2

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