Acetic Acid → (2R,4S)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluoro-benzyl)-2,2-dimethyl-oxazolidin-5-yl]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 732595Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 732595
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[C:15]([O:19][C:20]([N:22]1[CH2:26][C@H:25]([OH:27])[CH2:24][C@@H:23]1[C@H:28]1[O:32][C:31]([CH3:34])([CH3:33])[N:30]([C:35](=[O:37])[CH3:36])[C@H:29]1[CH2:38][C:39]1[CH:44]=[C:43]([F:45])[CH:42]=[C:41]([F:46])[CH:40]=1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C(O)(=O)C.C[Si](C)(C)CCOC(=O)C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C.O>[C:15]([O:19][C:20]([N:22]1[CH2:26][C@@H:25]([OH:27])[CH2:24][C@@H:23]1[C@H:28]1[O:32][C:31]([CH3:33])([CH3:34])[N:30]([C:35](=[O:37])[CH3:36])[C@H:29]1[CH2:38][C:39]1[CH:40]=[C:41]([F:46])[CH:42]=[C:43]([F:45])[CH:44]=1)=[O:21])([CH3:16])([CH3:17])[CH3:18]

Komponenten

10

Edukt 6

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 2724141Tetrabutylammonium FluorideHCID 112582822-(Trimethylsilyl)ethyl 4-(diphenylphosphino)benzoateHCID 68814386(2R,4R)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluorobenzyl)-2,2-dimethyloxazolidin-5-yl]-4-hydroxypyrrolidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 68814265(2R,4S)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluoro-benzyl)-2,2-dimethyl-oxazolidin-5-yl]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl esterAusbeute 95 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Add dropwise diisopropyl azodicarboxylate (0.20 mL, 1.04 mmol) to a solution of (2R,4R)-2-[(4S,5S)-3-acetyl-4-(3,5-difluorobenzyl)-2,2-dimethyloxazolidin-5-yl]-4-hydroxypyrrolidine-1-carboxylic acid tert-butyl ester (0.314 g, 0.69 mmol), acetic acid (0.06 mL, 1.04 mmol) and 4-diphenylphosphanyl-benzoic acid 2-trimethylsilanyl-ethyl ester (0.42 g, 1.04 mmol, prepared according to Synlett 2003 (4) p 473-476) in tetrahydrofuran (3 mL). Stir solution 18 hours, then add a 1M solution of tetrabutylammonium fluoride in tetrahydrofuran (3 mL) and stir 90 minutes. Add a 1N aqueous solution of sodium hydroxide (3 mL) and stir 30 minutes. Dilute with ethyl acetate and water. Evaporate the organic layer and dissolve in methanol (30 mL). Add sodium carbonate (0.365 g) and water (1 mL) and stir 18 hours. Evaporate and partition with ethyl acetate and water, wash organic layer with saturated sodium chloride solution, dry with magnesium sulfate and purify on silica gel with hexane/ethyl acetate mixtures to give the title compound as a foam (0.295 g, 95%).

Aufarbeitung

  1. stirringstir 30 minutes
  2. customEvaporate the organic layer
  3. dissolutiondissolve in methanol (30 mL)
  4. stirringAdd sodium carbonate (0.365 g) and water (1 mL) and stir 18 hours
  5. customEvaporate
  6. custompartition with ethyl acetate and water
  7. washwash organic layer with saturated sodium chloride solution
  8. dry with materialdry with magnesium sulfate
  9. custompurify on silica gel with hexane/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-8eede0e995b049db9ef5802cd1fb1ee2
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07585885B2

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