Sodium hydride → HCID 22049545, compound

HRID 2087148Notes

Reaction equation

HRID 2087148 reaction equation
[H-].[Na+].C([O:7][C:8](=[O:21])[NH:9][CH:10]([C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[C:15]([F:20])[CH:14]=1)[CH2:11]O)(C)(C)C>C1COCC1>[F:19][C:17]1[CH:18]=[C:13]([CH:10]2[CH2:11][O:21][C:8](=[O:7])[NH:9]2)[CH:14]=[C:15]([F:20])[CH:16]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 22048622HCID 22048622, compound

Product 1

HCID 22049545HCID 22049545, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Into a well-stirred suspension of NaH (1.1 g, 45.8 mmol) in THF (40 mL) at R.T. was added a solution of [1-(3,5-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-(3,5-difluorophenyl)-oxazolidin-2-one as a white flaky solid (2.8 g, 77% yield). M.P. 81-83° C.; 1H NMR (300 MHz, CDCl3) δ 7.23-7.03 (m, 3H), 6.08 (br s, 1H), 4.94 (dd, J=6.6 Hz, J=8.7 Hz, 1H), 4.73 (t, J=8.7 Hz, 1H), 4.13 (dd, J=6.6 Hz, J=8.7 Hz, 1H). The enantiomers were separated by HPLC on a Chiralcel OD (20×250 mm) column using 80% hexane/20% isopropyl alcohol as the eluting system at 12.0 mL/min (U.V. 254 nm). The retention times for the two isomers were 16.19 min and 20.08 min respectively.

Workup

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

Sources & evidence

ORD record
ord-d6285429615547b58344594b8707b846
Source dataset
uspto-grants-2004_04
Patent number
US06727264B1

Reaction notes

Loading…