Pivaloyl chloride → (4R,5S)-3-[3-(2,4-Difluoro-phenyl)-propionyl]-4-methyl-5-phenyl-oxazolidin-2-one

HRID 349816

Reaction equation

HRID 349816 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]([OH:13])=O.CC(C)(C)C(Cl)=O.[Li+].[Cl-].[CH3:23][C@H:24]1[C@@H:28]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[O:27][C:26](=[O:35])[NH:25]1>C(N(CC)CC)C.C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]([N:25]1[C@H:24]([CH3:23])[C@H:28]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[O:27][C:26]1=[O:35])=[O:13]

Participants

7

Reactant 4

HCID 62493Pivaloyl chlorideHCID 433294Lithium ChlorideHCID 8531614-Methyl-5-phenyl-2-oxazolidinone, (4S,5R)-HCID 49863953-(2,4-difluorophenyl)propanoic Acid

Product 1

HCID 69267110(4R,5S)-3-[3-(2,4-Difluoro-phenyl)-propionyl]-4-methyl-5-phenyl-oxazolidin-2-oneYield 99%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

A flask was charged with 29.5 g (158 mmol) of 3-(2,4-difluoro-phenyl)-propionic acid, 700 mL of THF, and 82.8 mL of triethylamine. The mixture was cooled to 0° C. and 23.4 mL of trimethyl acetyl chloride was added slowly. The mixture was stirred cold for 1 hour. Then 8.06 g (190 mmol) of LiCl and 28.1 g of (4S,5R)-4-methyl-5-phenyl-oxazolidin-2-one was added. The mixture was allowed to warm room temperature and stirred overnight. The solids were filtered off, and the solvent was removed under reduced pressure. The residue was taken up in diethyl ether and washed with sat. aq. ammonium chloride, sat. aq. sodium bicarbonate, and the solvent was removed under reduced pressure. The crude residue was purified by column chromatography (3:1 dichloromethane/hexanes eluent) to give 54 g (99% yield) of the titled compound.

Workup

  1. temperatureto warm room temperature
  2. stirringstirred overnight
  3. filtrationThe solids were filtered off
  4. customthe solvent was removed under reduced pressure
  5. washwashed with sat. aq. ammonium chloride, sat. aq. sodium bicarbonate
  6. customthe solvent was removed under reduced pressure
  7. customThe crude residue was purified by column chromatography (3:1 dichloromethane/hexanes eluent)

Sources & evidence

ORD record
ord-dd064df9909948a089c4e4418d5126f0
Source dataset
uspto-grants-2007_02
Patent number
US07179934B2

Linked notes

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