3-(4-(3(S)-(2-Methoxyethoxycarbonylamino)pyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloroethyloxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one → 3-(4-(3(S)-(2-Methoxyethoxycarbonylamino)pyrrolidin-1-yl)-3-fluorophenyl)-5(S)-(isoxazol-3-ylaminomethyl)oxazolidin-2-one

HRID 1582351Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1582351
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23]([CH2:25][N:26]([C:35]4[CH:39]=[CH:38][O:37][N:36]=4)C(OCC(Cl)(Cl)Cl)=O)[O:22][C:21]3=[O:40])=[CH:16][C:15]=2[F:41])[CH2:10]1)=[O:7]>C(O)(=O)C.O.[Zn]>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23]([CH2:25][NH:26][C:35]4[CH:39]=[CH:38][O:37][N:36]=4)[O:22][C:21]3=[O:40])=[CH:16][C:15]=2[F:41])[CH2:10]1)=[O:7]

Komponenten

5

Edukt 1

HCID 695847543-(4-(3(S)-(2-Methoxyethoxycarbonylamino)pyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloroethyloxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one

Produkt 1

HCID 695848763-(4-(3(S)-(2-Methoxyethoxycarbonylamino)pyrrolidin-1-yl)-3-fluorophenyl)-5(S)-(isoxazol-3-ylaminomethyl)oxazolidin-2-oneAusbeute 48,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23994ZincKatalysatorHCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

3-(4-(3(S)-(2-Methoxyethoxycarbonylamino)pyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloroethyloxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one (400 mg, 0.5 mM) was stirred in a mixture of acetic acid (10 ml) and water (2 ml). Zinc dust (203 mg, 3.1 mM) was added, and the mixture stirred 30 minutes at ambient temperature. The mixture was filtered through celite, and the residue after evaporation partitioned between ethyl acetate (10 ml) and aqueous sodium bicarbonate (15 ml). The organic phase was washed with sodium bicarbonate (2×15 ml), water (15 ml), dried (magnesium sulfate), and evaporated. The crude product was purified by chromatography on a 10 g Biotage silica column, eluting with a gradient from dichloromethane to ethyl acetate. Relevant fractions were combined to give the desired product (141 mg ). NMR (DMSO-d6) δ: 1.83 (hextet, 1H); 2.09 (hextet, 1H); 3.13 (m, 1H); 3.26 (s, 3H); 3.40, 3.47 (t overlapping m, 7H); 3.73 (dd, 1H); 4.04 (overlapping m, 4H); 4.82 (m, 1H); 6.01 (d, 1H); 6.52 (t, 1H); 6.72 (t, 1H); 7.08 (dd, 1H); 7.39 (dd, 1H); 7.52 (d, 1H); 8.37 (d, 1H). MS (ESP): 464 (MH+) for C21H26FN5O6

Aufarbeitung

  1. filtrationThe mixture was filtered through celite
  2. customthe residue after evaporation
  3. custompartitioned between ethyl acetate (10 ml) and aqueous sodium bicarbonate (15 ml)
  4. washThe organic phase was washed with sodium bicarbonate (2×15 ml), water (15 ml)
  5. dry with materialdried (magnesium sulfate)
  6. customevaporated
  7. customThe crude product was purified by chromatography on a 10 g Biotage silica column
  8. washeluting with a gradient from dichloromethane to ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-e542bc20bf2f48f48b0bfb2b97b1b2d8
Quelldatensatz
uspto-grants-2004_05
Patentnummer
US06734200B1

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