2,3-Dihydroxybutanedioic Acid → 4-[5-(4-Fluorophenyl)-1-(4-fluorophenylamino)-5-hydroxy-2-(2-oxo-4-phenyloxazolidine-3-carbonyl)-pentyl]-benzonitrile

HRID 1612515

Reaktionsgleichung

Reaktionsgleichung von HRID 1612515
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:26])[CH2:9][CH2:10][CH2:11][C:12]([N:14]2[CH:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:17][O:16][C:15]2=[O:25])=[O:13])=[CH:4][CH:3]=1.[F:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]=[CH:35][C:36]2[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=2)=[CH:30][CH:29]=1.C(N(C(C)C)CC)(C)C.C[Si](Cl)(C)C.C(O)(=O)C(C(C(O)=O)O)O.C(=O)(O)[O-].[Na+]>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:26])[CH2:9][CH2:10][CH:11]([C:12]([N:14]2[CH:18]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:17][O:16][C:15]2=[O:25])=[O:13])[CH:35]([C:36]2[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=2)[NH:34][C:31]2[CH:30]=[CH:29][C:28]([F:27])=[CH:33][CH:32]=2)=[CH:4][CH:3]=1

Komponenten

9

Edukt 6

HCID 8752,3-Dihydroxybutanedioic AcidHCID 6397ChlorotrimethylsilaneHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9135414-[(4-Fluoro-phenylimino)methyl]benzonitrileHCID 121116173-[5-(4-Fluorophenyl)-5-hydroxy-1-oxopentyl]-4-phenyl-2-oxazolidinone

Produkt 1

HCID 222520644-[5-(4-Fluorophenyl)-1-(4-fluorophenylamino)-5-hydroxy-2-(2-oxo-4-phenyloxazolidine-3-carbonyl)-pentyl]-benzonitrile

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24193Titanium TetrachlorideKatalysatorHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
-10 °C

Versuchsvorschrift

Under argon, 2.5 g of 3-[5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-oxazolidin-2-one are dissolved in 30 ml of dichloromethane, 3.9 g of 4-[(4-fluoro-phenylimino)methyl]benzonitrile are added and the mixture is cooled to −10° C. 6.4 ml of diisopropylethylamine are added to this mixture and then, over a period of 3 min, 4.05 ml of trimethylsilyl chloride such that the temperature does not exceed −5° C. At this temperature, the mixture is stirred for another hour, and it is then cooled to −25° C. 0.8 ml of titanium tetrachloride is then added slowly. The dark mixture is stirred at −25 to −30° C. overnight and then decomposed using 35 ml of 7% strength tartaric acid solution, and stirring is continued at room temperature for 1 hour. 15 ml of a 20% strength sodium bicarbonate solution are then added, and the mixture is stirred for another hour. Following phase separation, the org. phase is washed with 30 ml of water, dried over magnesium sulfate and concentrated to about 10 ml. After addition of 2 ml of bistrimethylsilylacetamide, the mixture is heated at reflux for 30 min and then concentrated under reduced pressure. The residue is crystallized with ethyl acetate/heptane. The product is filtered off with suction and dried under reduced pressure. This gives 5 of molecular weight 653.81 (C37H37F2N3O4Si); MS (ESI+): 654.3 (M+H+), 582.2 (M+H+—Si(CH3)3).

Aufarbeitung

  1. customdoes not exceed −5° C
  2. temperatureit is then cooled to −25° C
  3. stirringThe dark mixture is stirred at −25 to −30° C. overnight
  4. stirringstirring
  5. waitis continued at room temperature for 1 hour
  6. stirringthe mixture is stirred for another hour
  7. customFollowing phase separation
  8. washphase is washed with 30 ml of water
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated to about 10 ml
  11. additionAfter addition of 2 ml of bistrimethylsilylacetamide
  12. temperaturethe mixture is heated
  13. temperatureat reflux for 30 min
  14. concentrationconcentrated under reduced pressure
  15. customThe residue is crystallized with ethyl acetate/heptane
  16. filtrationThe product is filtered off with suction
  17. customdried under reduced pressure
  18. customThis gives 5 of molecular weight 653.81 (C37H37F2N3O4Si)

Quellen und Nachweise

ORD-Eintrag
ord-657c7f45d5ad44e290d069142cf70b0c
Quelldatensatz
uspto-grants-2006_01
Patentnummer
US06992067B2

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