Water → 4-(3,4-Difluorophenyl)-5-methyl-oxazolidin-2-one

HRID 2087154Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2087154
C([O:5][C:6](=[O:20])[NH:7][CH:8]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([F:19])[CH:13]=1)[CH:9](O)[CH3:10])(C)(C)C.[H-].[Na+].O>C1COCC1>[F:19][C:14]1[CH:13]=[C:12]([CH:8]2[CH:9]([CH3:10])[O:20][C:6](=[O:5])[NH:7]2)[CH:17]=[CH:16][C:15]=1[F:18]

Komponenten

5

Edukt 3

HCID 962WaterHCID 24758Sodium hydride2×HCID 22048785[1-(3,4-Difluorophenyl)-2hydroxy-propyl]-carbamic acid-tert-butyl ester

Produkt 1

HCID 220486254-(3,4-Difluorophenyl)-5-methyl-oxazolidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
35 °C

Versuchsvorschrift

Into a well-stirred solution of [1-(3,4-difluorophenyl)-2-hydroxy-propyl]-carbamic acid-tert-butyl ester (0.43 g, 1.5 mmol) in THF (20 mL) was added 95% NaH (0.09 g, 3.8 mmol) at room temperature. When the reaction was carried out on a larger (>5 g) scale, 1.0 equivalent of KH and 1.5 eq. of NaH was used as the base. The resulting suspension was stirred for 3 h at about 35° C. (warm water bath) and then quenched carefully with ice. The biphasic mixture was extracted with 100 mL of EtOAc, washed with brine, dried over Na2SO4, filtered and the solvent was removed in vacuo. The two diastereomers were separated by column chromatography over silica gel (First isomer: 0.16 g, Rf=0.6, 3:1 hexane-EtOAc; second isomer: 0.18 g, Rf=0.5, 3:1 hexane-EtOAc). NOE experiments suggested that the first diastereomer had the methyl and the aryl group in trans configuration while the second diastereomer had cis relationship between the two groups. The 1H NMR spectrum for the trans diastereomer is as follows. 1H NMR (CDCl3) δ 1.49 (d, J=6.0 Hz, 3H), 4.37 (dq, J=6.0 Hz, J=7.2 Hz, 1H), 4.45 (d, J=7.2 Hz, 1H), 6.63 (br s, 1H), 7.08-7.28 (m, 3H).

Aufarbeitung

  1. customquenched carefully with ice
  2. extractionThe biphasic mixture was extracted with 100 mL of EtOAc
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo
  7. customThe two diastereomers were separated by column chromatography over silica gel (First isomer: 0.16 g, Rf=0.6, 3:1 hexane-EtOAc; second isomer: 0.18 g, Rf=0.5, 3:1 hexane-EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-bf98b9b758524d79a9eb3a6bb448b7dc
Quelldatensatz
uspto-grants-2004_04
Patentnummer
US06727264B1

Notizen zur Reaktion

Wird geladen…