Methanol → (S)-N-[[3-(3-Fluorophenyl)-2-oxo-5-oxazolidinyl]methyl]acetamide

HRID 2180346

Reaktionsgleichung

Reaktionsgleichung von HRID 2180346
CC(C)COC(=O)[NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[CH:8]=1.[C:16]([O:19][C@H:20]([CH2:26]Cl)[CH2:21][NH:22][C:23](=[O:25])[CH3:24])(=[O:18])C.CO.[Cl-].[NH4+]>CCCCCCC.C1(C)C=CC=CC=1.O.CN(C)C=O>[F:13][C:9]1[CH:8]=[C:7]([N:6]2[CH2:26][C@H:20]([CH2:21][NH:22][C:23](=[O:25])[CH3:24])[O:19][C:16]2=[O:18])[CH:12]=[CH:11][CH:10]=1

Komponenten

9

Edukt 4

HCID 887MethanolHCID 25517Ammonium ChlorideHCID 7357675(2S)-1-Acetamido-3-chloropropan-2-yl acetateHCID 159082813-Fluorophenylcarbamic acid 2-methylpropyl ester

Produkt 1

HCID 11345751(S)-N-[[3-(3-Fluorophenyl)-2-oxo-5-oxazolidinyl]methyl]acetamideAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8900HeptaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
1.5 °C

Versuchsvorschrift

To a mixture of 3-fluorophenylcarbamic acid 2-methylpropyl ester (300.0 g, 1.42 mol), (S)-N-[2-(acetyloxy)-3-chloropropyl]acetamide (556.1 g, 2.87 mol, 2.02 eq), methanol (90.03 g, 2.81 mol, 1.98 eq) and N,N-dimethylformamide (500 ml) is added a slurry of lithium t-amylate (401.3 g, 4.27 mol, 3.00 eq) in heptane (1 liter) while maintaining −4 to 7° C., followed by heptane (100 ml). The mixture is then stirred at 19 to 20° C. for 21 h. The reaction mixture is then added to a mixture of ammonium chloride (228 g, 4.26 mol, 3.00 eq), water (2.0 liter) and toluene (1.0 liter) while maintaining 8 to 10° C. The reaction mixture is rinsed in with a mixture of water (100 ml), saturated ammonium chloride (50 ml) and toluene (100 ml). The precipitate is collected by vacuum filtration and washed with heptane (1 liter) and water (1 liter) and dried in a nitrogen stream to give 252.4 g of crude product. This is triturated in acetonitrile (1 kg) at 90° C. and the slurry concentrated under reduced pressure to 800 ml total volume. Toluene (1900 ml) is added while concentrating to maintain 800 ml total volume. Water (1 liter) and heptane (1 liter) are added and the precipitate collected by vacuum filtration, washed with water (750 ml) and heptane (250 ml) and dried in a nitrogen stream to give the title compound (225.7 g, 63.0%).

Aufarbeitung

  1. temperaturewhile maintaining 8 to 10° C
  2. washThe reaction mixture is rinsed in with a mixture of water (100 ml), saturated ammonium chloride (50 ml) and toluene (100 ml)
  3. filtrationThe precipitate is collected by vacuum filtration
  4. washwashed with heptane (1 liter) and water (1 liter)
  5. customdried in a nitrogen stream
  6. customto give 252.4 g of crude product
  7. customThis is triturated in acetonitrile (1 kg) at 90° C.
  8. concentrationthe slurry concentrated under reduced pressure to 800 ml total volume
  9. additionToluene (1900 ml) is added
  10. concentrationwhile concentrating
  11. temperatureto maintain 800 ml total volume
  12. additionWater (1 liter) and heptane (1 liter) are added
  13. filtrationthe precipitate collected by vacuum filtration
  14. washwashed with water (750 ml) and heptane (250 ml)
  15. customdried in a nitrogen stream

Quellen und Nachweise

ORD-Eintrag
ord-3272fe83bc6d41b59445cc6198127e21
Quelldatensatz
uspto-grants-2005_05
Patentnummer
US06887995B2

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