Carbon Dioxide → HCID 53853142, Verbindung

HRID 1418659Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1418659
[F:1][C:2]1[CH:3]=[C:4]([N:15]2[CH2:19][C@@H:18]([CH2:20]CS([O-])(=O)=O)[O:17][C:16]2=[O:26])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:11][C:10]([O:13][CH3:14])([CH3:12])[CH2:9]1.[OH-].[NH4+].[CH:29]([OH:32])(C)[CH3:30].C(=O)=O.S([O-])(=O)(=O)C.[N:41]1C=CC=CC=1.C(OC(=O)C)(=O)C.O1CCNC1=O>CO.C(Cl)(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([N:15]2[CH2:19][C@H:18]([CH2:20][NH:41][C:29](=[O:32])[CH3:30])[O:17][C:16]2=[O:26])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:9][C:10]([O:13][CH3:14])([CH3:12])[CH2:11]1

Komponenten

9

Edukt 7

HCID 280Carbon DioxideHCID 1049PyridineHCID 7918Acetic AnhydrideHCID 739492-OxazolidinoneHCID 85257MethanesulfonateHCID 22611478Ammonium hydroxide isopropanolHCID 86753889HCID 86753889, Verbindung

Produkt 1

HCID 53853142HCID 53853142, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21584188Chloroform methanolLösungsmittel

Versuchsvorschrift

A mixture of (R)-[[3-[3-fluoro-4-(3-methoxy-3-methyl1-azetidinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]methanesulfonate (0.680 g, 1.75 mmol) in 2:1 ammonium hydroxide/isopropanol (30 mL) was heated to reflux (dry-ice condenser). TLC analysis (5% methanol/chloroform) after 7 hours revealed mostly starting material. The reaction was continued for an additional 46 hours. After cooling to ambient temperature, TLC indicated that the starting mesylate was essentially consumed. The reaction mixture was transferred to a separatory funnel, along with dichloromethane (100 mL), and washed with water. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The crude 5-(atminomethyl)oxazolidinone was dissolved in dry dichloromethane (10 mL), cooled to 0° C. with an ice bath, and treated with pyridine (0.698 g, 0.708 mL, 8.75 mmol) and acetic anhydride (0.357 g, 0.330 mL, 3.50 mmol). The cooling bath was then removed and the reaction mixture stirred at ambient temperature overnight. The reaction mixture was diluted with additional dichloromethane (60 mL) and washed with 5% aqueous hydrochloric acid, saturated aqueous sodium carbonate, water and brine. The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to give a crude gum. Radial chromatography over silica gel, eluting with 1%, 2% and 4% methanol/chloroform afforded, after concentration of appropriate fractions, 0.481 g (78%) of the title oxazolidinone antibacterial agent as a white foamy solid. A lyophilized sample had mp 132°-134° C. and MS(EI) 351 (M+).

Aufarbeitung

  1. temperaturewas heated
  2. customwas essentially consumed
  3. customThe reaction mixture was transferred to a separatory funnel, along with dichloromethane (100 mL)
  4. washwashed with water
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe crude 5-(atminomethyl)oxazolidinone was dissolved in dry dichloromethane (10 mL)
  9. temperaturecooled to 0° C. with an ice bath
  10. customThe cooling bath was then removed
  11. additionThe reaction mixture was diluted with additional dichloromethane (60 mL)
  12. washwashed with 5% aqueous hydrochloric acid, saturated aqueous sodium carbonate, water and brine
  13. dry with materialThe organic layer was then dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customto give a crude gum
  17. washRadial chromatography over silica gel, eluting with 1%, 2% and 4% methanol/chloroform
  18. customafforded

Quellen und Nachweise

ORD-Eintrag
ord-5aa02fbbd0b2443cbd3e60f7085e774e
Quelldatensatz
uspto-grants-1999_03
Patentnummer
US05883093

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