Water → (4RS,5SR)-5-(2,4-difluorophenyl)-4-((4-(trifluoromethyl)phenyl)methyl)-1,3-oxazolidin-2-one

HRID 1610388Notes

Reaction equation

HRID 1610388 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9](O)[CH:10]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1)C(O)=O.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:33])C=CC=CC=1.C([N:45]([CH2:48]C)CC)C.[OH2:50]>O1CCCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[O:50][C:48](=[O:33])[NH:45][CH:10]1[CH2:14][C:15]1[CH:16]=[CH:17][C:18]([C:21]([F:23])([F:24])[F:22])=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 22261837(2RS,3RS)-3-(2,4-difluorophenyl)-3-hydroxy-2-((4-(trifluoromethyl)phenyl)methyl)propionic acid

Product 1

HCID 22261917(4RS,5SR)-5-(2,4-difluorophenyl)-4-((4-(trifluoromethyl)phenyl)methyl)-1,3-oxazolidin-2-oneYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2RS,3RS)-3-(2,4-difluorophenyl)-3-hydroxy-2-((4-(trifluoromethyl)phenyl)methyl)propionic acid (5.0 g, 13.9 mmol) in tetrahydrofuran (150 ml) were added diphenylphosphoryl azide (3.3 ml, 15.3 mmol) and triethylamine (2.9 ml, 20.8 mmol) and the mixture was heated under reflux for 6 hrs. The reaction solution was allowed to stand at room temperature, water (200 ml) was added, and the mixture was extracted with ethyl acetate (200 ml×2). The extract was washed successively with 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate). The residue was recrystallized from ethyl acetate-hexane to give (4RS,5SR)-5-(2,4-difluorophenyl)-4-((4-(trifluoromethyl)phenyl)methyl)-1,3-oxazolidin-2-one (3.86 g, 78%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 6 hrs
  3. customto stand at room temperature
  4. extractionthe mixture was extracted with ethyl acetate (200 ml×2)
  5. washThe extract was washed successively with 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (ethyl acetate)
  9. customThe residue was recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-c843336df024453ea49d4a8ac21a693e
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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