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

HRID 1167687Notes

Reaction equation

HRID 1167687 reaction equation
[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]

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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 THF 20 mL via a dropping funnel at room temperature. The resulting suspension was stirred for 3 h 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%). The enantiomers were separated by using Chiralcel OD (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); Anal. Calcd. 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); Anal. Calcd. 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.

Workup

  1. stirringThe resulting suspension was stirred for 3 h
  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)

Sources & evidence

ORD record
ord-cd4aaf02b9a44df5b80f5e7bfb01ef10
Source dataset
uspto-grants-2003_09
Patent number
US06620815B1

Reaction notes

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