5(R)-(N-(2,2,2-Trichloroethyloxycarbonyl)-isoxazol-3-ylaminomethyl)-3-(4-imidazol-1-yl-3-fluorophenyl)oxazolidin-2-one → (5S)-3-(3-fluoro-4-imidazol-1-yl-phenyl)-5-[(isoxazol-3-ylamino)methyl]oxazolidin-2-one

HRID 1582332

Reaktionsgleichung

Reaktionsgleichung von HRID 1582332
ClC(Cl)(Cl)COC([N:7]([CH2:13][C@@H:14]1[O:18][C:17](=[O:19])[N:16]([C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH:30]=[CH:29][N:28]=[CH:27]3)=[C:22]([F:31])[CH:21]=2)[CH2:15]1)[C:8]1[CH:12]=[CH:11][O:10][N:9]=1)=O>C(O)(=O)C.O.[Zn]>[O:10]1[CH:11]=[CH:12][C:8]([NH:7][CH2:13][C@@H:14]2[O:18][C:17](=[O:19])[N:16]([C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH:30]=[CH:29][N:28]=[CH:27]4)=[C:22]([F:31])[CH:21]=3)[CH2:15]2)=[N:9]1

Komponenten

5

Edukt 1

HCID 571687335(R)-(N-(2,2,2-Trichloroethyloxycarbonyl)-isoxazol-3-ylaminomethyl)-3-(4-imidazol-1-yl-3-fluorophenyl)oxazolidin-2-one

Produkt 1

HCID 497417(5S)-3-(3-fluoro-4-imidazol-1-yl-phenyl)-5-[(isoxazol-3-ylamino)methyl]oxazolidin-2-oneAusbeute 41,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23994ZincKatalysator2×HCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

5(R)-(N-(2,2,2-Trichloroethyloxycarbonyl)-isoxazol-3-ylaminomethyl)-3-(4-imidazol-1-yl-3-fluorophenyl)oxazolidin-2-one (crude, 1.7 g, ˜2.5 mM), was stirred in a mixture of acetic acid (40 ml) and water (18 ml) under nitrogen at ambient temperature. Zinc dust (824 mg, 12.5 mM) was added, the mixture stirred 20 minutes, a further portion (200 mg ) of zinc added, and stirring continued for 1 hour. The mixture was filtered through celite, and the filter pad washed well with a mixture of acetic acid and water (5:1). The filtrates were evaporated, and the residue partitioned between hydrochloric acid (0.5 M, 200 ml) and dichloromethane (150 ml). The aqueous phase was washed with dichloromethane (100 ml), then made basic with the minimum quantity of concentrated ammonia solution, re-extracted with dichloromethane (2×150 ml), dried (magnesium sulfate), and evaporated. Recrystallisation from isopropanol (40 ml) gave the desired product (470 mg ). NMR (DMSO-d6) δ: 3.46 (t, 2H); 3.87 (dd, 1H); 4.21 (t, 1H); 4.92 (m, 1H); 6.01 (d, 1H); 6.53 (t, 1H); 7.12 (t, 1H); 7.46 (dd, 1H); 7.53 (d, 1H); 7.66 (t, 1H); 7.74 (dd, 1H); 7.98 (m, 1H); 8.39 (d, 1H). MS (ESP): 362 (MH+) for C16H14FN5O3

Aufarbeitung

  1. stirringstirring
  2. waitcontinued for 1 hour
  3. filtrationThe mixture was filtered through celite
  4. washthe filter pad washed well with a mixture of acetic acid and water (5:1)
  5. customThe filtrates were evaporated
  6. customthe residue partitioned between hydrochloric acid (0.5 M, 200 ml) and dichloromethane (150 ml)
  7. washThe aqueous phase was washed with dichloromethane (100 ml)
  8. extractionre-extracted with dichloromethane (2×150 ml)
  9. dry with materialdried (magnesium sulfate)
  10. customevaporated
  11. customRecrystallisation from isopropanol (40 ml)

Quellen und Nachweise

ORD-Eintrag
ord-2e13352ce45b4901b2f937897b1b0cec
Quelldatensatz
uspto-grants-2004_05
Patentnummer
US06734200B1

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