Ammonia → Avibactam Impurity 19

HRID 1620463Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1620463
[CH2:1]([O:8][N:9]1[C:15](=[O:16])[N:14]2[CH2:17][C@@H:10]1[CH2:11][CH2:12][C@@H:13]2[C:18]([OH:20])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([N:23](CC)CC)C.ClC(OCC(C)C)=O.N>ClCCl.CCCCCC.C(OCC)(=O)C.O>[CH2:1]([O:8][N:9]1[C:15](=[O:16])[N:14]2[CH2:17][C@@H:10]1[CH2:11][CH2:12][C@@H:13]2[C:18]([NH2:23])=[O:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Komponenten

8

Edukt 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 66870454(2R,5S)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid

Produkt 1

HCID 66870463Avibactam Impurity 19Ausbeute 87,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 21226206Ethyl acetate hexaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

230 mg (0.84 mmol) of (2R,5S)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid was dissolved in dehydrated dichloromethane (4.2 mL), and 110 mg of triethylamine was added, followed by cooling to 0° C. 137 mg of isobutyl chloroformate was added to the mixture, followed by stirring at the same temperature for 20 minutes, 0.6 mL of aqueous ammonia was added to the reaction mixture, followed by stirring at room temperature for 1 hour. Subsequently, water (10 mL) was added and the organic layer was aliquoted, followed by sequential washing with water and saturated brine and drying over anhydrous magnesium sulfate. The residue resulting from concentration of the solvent under reduced pressure was applied to silica gel column chromatography (hexane/ethyl acetate=1/3), and subsequently crystallized with chloroform/hexane=1:3 to afford 202 mg of the title compound as a colorless crystalline powder (yield 87%). Enantiomeric excess: 99.9% ee or more (CHIRALPAK AD-H, 4.6×150 mm, hexane/ethanol=4/1. UV 210 nm, flow rate 1 mL/min., retention time 10.3 min.).

Aufarbeitung

  1. stirringby stirring at room temperature for 1 hour
  2. washby sequential washing with water and saturated brine
  3. dry with materialdrying over anhydrous magnesium sulfate
  4. customThe residue resulting from concentration of the solvent under reduced pressure
  5. customsubsequently crystallized with chloroform/hexane=1:3

Quellen und Nachweise

ORD-Eintrag
ord-422032128f5f4cf781dce35c59c1f5c4
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772490B2

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