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

HRID 1610475Notes

Reaction equation

HRID 1610475 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([CH:13]([OH:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)C(O)=O)=[CH:4][CH:3]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:32])C=CC=CC=1.C([N:44]([CH2:47]C)CC)C>O1CCCC1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH:9]2[CH:13]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:21])([F:23])[F:22])=[CH:16][CH:15]=3)[O:24][C:47](=[O:32])[NH:44]2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 17862204(2RS,3RS)-2-((4-fluorophenyl)methyl)-3-hydroxy-3-(4-(trifluoromethyl)phenyl)propionic acid

Product 1

HCID 22261770(4RS,5SR)-4-((4-fluorophenyl)methyl)-5-(4-(trifluoromethyl)phenyl)-1,3-oxazolidin-2-oneYield 92.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2RS,3RS)-2-((4-fluorophenyl)methyl)-3-hydroxy-3-(4-(trifluoromethyl)phenyl)propionic acid (21.0 g, 61.35 mmol) in tetrahydrofuran (500 ml) were added diphenylphosphoryl azide (14.5 ml, 67.5 mmol) and triethylamine (12.9 ml, 92 mmol), and the mixture was heated under reflux for 3 hrs. The reaction solution was diluted with water (500 ml), and the mixture was extracted with ethyl acetate (500 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate). Recrystallization from ethyl acetate-hexane gave (4RS,5SR)-4-((4-fluorophenyl)methyl)-5-(4-(trifluoromethyl)phenyl)-1,3-oxazolidin-2-one (19.24 g, 92%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 3 hrs
  3. extractionthe mixture was extracted with ethyl acetate (500 ml×2)
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customevaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate)
  8. customRecrystallization from ethyl acetate-hexane

Sources & evidence

ORD record
ord-b9ff729f76d349ce8b92eb413db3da33
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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