(2S)-1-Acetamido-3-chloropropan-2-yl acetate → (-)-N-[[(5S)-3-(3,4-dihydro-1H-2-benzothiopyran-6-yl)-2-oxo-5-oxazolidinyl]methyl]acetamide

HRID 488369

Reaktionsgleichung

Reaktionsgleichung von HRID 488369
[CH2:1]1[C:6]2[CH:7]=[CH:8][C:9]([NH:11]C(=O)OCC3C=CC=CC=3)=[CH:10][C:5]=2[CH2:4][CH2:3][S:2]1.[C:22]([O:25][C@H:26]([CH2:32]Cl)[CH2:27][NH:28][C:29](=[O:31])[CH3:30])(=[O:24])C.O(C(C)(C)C)[Li]>CN(C=O)C.CO.CC(O)=O>[CH2:1]1[C:6]2[CH:7]=[CH:8][C:9]([N:11]3[CH2:32][C@H:26]([CH2:27][NH:28][C:29](=[O:31])[CH3:30])[O:25][C:22]3=[O:24])=[CH:10][C:5]=2[CH2:4][CH2:3][S:2]1

Komponenten

7

Edukt 3

HCID 7357675(2S)-1-Acetamido-3-chloropropan-2-yl acetateHCID 86585912phenylmethyl (3,4-dihydro-1H-2-benzothiopyran-6-yl)carbamateHCID 178506942HCID 178506942, Verbindung

Produkt 1

HCID 60054141(-)-N-[[(5S)-3-(3,4-dihydro-1H-2-benzothiopyran-6-yl)-2-oxo-5-oxazolidinyl]methyl]acetamideAusbeute 73 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 176Acetic AcidLösungsmittelHCID 887MethanolLösungsmittel2×HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of phenylmethyl (3,4-dihydro-1H-2-benzothiopyran-6-yl)carbamate (Step 3, 2.55 g, 8.52 mmol), (1S)-2-(acetylamino)-1-(chloromethyl)ethyl acetate (Tet. Lett. 1996 37 (44) 7737-7740; 3.30 g, 17.03 mmol) and MeOH (0.690 mL, 17.03 mmol) in dry DMF (5.6 mL) under N2 is treated with LiOtBu (1M in hexanes, 25.5 mL, 25.5 mmol) dropwise over 2 hrs, and the resulting biphasic mixture is stirred at ambient temperature for 32 hrs. The mixture is then cooled in an ice bath and treated with glacial HOAc (975 μL), and MeOH (10 mL) is added and the layers are separated. The hexane layer is reextracted with 20% H2O/MeOH (20 mL), and the combined MeOH/H2O phase is diluted with H2O (40 mL) and extracted with EtOAc (3×40 mL). The combined EtOAc phase is then washed with H2O (2×50 mL) and brine (25 mL), dried over MgSO4 and concentrated under reduced pressure, and the residue is chromatographed on a Flash 40M silica gel (90 g, 32-63 μm) cartridge, eluting with a gradient of MeOH/CH2Cl2 (0.5/99.5-3/97). Those fractions with an Rf=0.27 by TLC (MeOH/CHCl3, 5/95) are pooled and concentrated and the product triturated with EtOAc/Et2O to give 1.90 g (73%) of the title compound as an off-white solid, mp 112-114° C. (decomp.). MS (ESI+) for C15H18N2O3S m/z 307 (M+H)+; [α]25D=−24° (c 0.80, DMSO).

Aufarbeitung

  1. temperatureThe mixture is then cooled in an ice bath
  2. additionis added
  3. customthe layers are separated
  4. additionthe combined MeOH/H2O phase is diluted with H2O (40 mL)
  5. extractionextracted with EtOAc (3×40 mL)
  6. washThe combined EtOAc phase is then washed with H2O (2×50 mL) and brine (25 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customthe residue is chromatographed on a Flash 40M silica gel (90 g, 32-63 μm) cartridge
  10. washeluting with a gradient of MeOH/CH2Cl2 (0.5/99.5-3/97)
  11. concentrationconcentrated
  12. customthe product triturated with EtOAc/Et2O

Quellen und Nachweise

ORD-Eintrag
ord-d907ed1789cd48cf89b9880e3e10bbf1
Quelldatensatz
uspto-grants-2005_12
Patentnummer
US06972286B2

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