Sodium hydride → 4-(3,4-Difluorophenyl)-1,3-oxazolidin-2-one

HRID 278901

Reaktionsgleichung

Reaktionsgleichung von HRID 278901
[H-].[Na+].C([O:7][C:8](=[O:21])[NH:9][CH:10]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=1)[CH2:11]O)(C)(C)C>C1COCC1>[F:20][C:15]1[CH:14]=[C:13]([CH:10]2[CH2:11][O:21][C:8](=[O:7])[NH:9]2)[CH:18]=[CH:17][C:16]=1[F:19]

Komponenten

4

Edukt 2

HCID 24758Sodium hydrideHCID 22049336Tert-butyl 1-(3,4-difluorophenyl)-2-hydroxyethylcarbamate

Produkt 1

HCID 220487464-(3,4-Difluorophenyl)-1,3-oxazolidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a well stirred suspension of NaH (1.1 g, 45.8 mmol) in THF (40 mL) at room temperature was added a solution of [1-(3,4-difluorophenyl)-2-hydroxy-ethyl]-carbamic acid-tert-butyl ester (5.0 g, 18.3 mmol) in 20 mL THF via a dropping funnel at room temperature. The resulting suspension was stirred for 3 hours and then quenched carefully with 10 mL of water. The biphasic mixture was extracted with 100 mL of Et2O, washed with brine, filtered, and the solvent was removed in vacuo. The gummy residue thus obtained was purified by column chromatography over silica gel (Rf=0.15, 3:2 hexane-EtOAc) to obtain 4-(3,4-difluorophenyl)-oxazolidin-2-one as a white flaky solid (2.8 g, 77%). M.P. 81-83° C.; 1H NMR δ4.13 (dd, J=6.6 Hz, J=8.7 Hz, 1 H), 4.73 (t, J=8.7 Hz, 1 H), 4.94 (dd, J=6.6 Hz, J=8.7 Hz, 1 H), 6.08 (br, s, 1 H), 7.03-7.23 (m, 3 H). The enantiomers were separated by using Chiralcel OD column (4.6×250 mm) using 80% hexane/20% isopropyl alcohol/0.1% diethylamine as the eluting system under isothermal conditions (U.V. 254 nM). The retention times for the two isomers were 16.19 min and 20.08 min respectively. First isomer: [α]D=+62.9 (c=0.67, acetone); Analysis calculated for C9H7NO2F2: C, 54.28; H, 3.54; N, 7.03. Found: C, 54.16; H, 3.44; N, 6.96. Second isomer: [α]D=−56.9 (c=0.75, acetone); Analysis calculated for C9H7NO2F2: C, 54.28; H, 3.54; N, 7.03. Found: C, 54.31; H, 3.46; N, 6.98. The first isomer was used in the next step.

Aufarbeitung

  1. stirringThe resulting suspension was stirred for 3 hours
  2. customquenched carefully with 10 mL of water
  3. extractionThe biphasic mixture was extracted with 100 mL of Et2O
  4. washwashed with brine
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo
  7. customThe gummy residue thus obtained
  8. customwas purified by column chromatography over silica gel (Rf=0.15, 3:2 hexane-EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-30c68dea0d3b48b6913e1bb0af6cf25a
Quelldatensatz
uspto-grants-2002_03
Patentnummer
US06362182B1

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