2-Methoxyphenylacetic acid → (4S,5S)-4-methyl5-Phenyl-3-(2-methoxyphenylacetyl)-2-oxazolidinone

HRID 1721212Notes

Reaction equation

HRID 1721212 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([OH:12])=O.[H-].[Na+].C(Cl)(=O)C(C)(C)C.C([Li])CCC.[CH3:27][C@H:28]1[C@H:32]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[O:31][C:30](=[O:39])[NH:29]1.[Cl-].[NH4+]>O1CCCC1.CCCCCC.C(OCC)(=O)C>[CH3:27][C@H:28]1[C@H:32]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[O:31][C:30](=[O:39])[N:29]1[C:10](=[O:12])[CH2:9][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[O:2][CH3:1]

Participants

10

Reactant 6

HCID 71342-Methoxyphenylacetic acidHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 62493Pivaloyl chlorideHCID 11095183(4S,5S)-4-Methyl-5-phenyl-2-oxazolidinoneHCID 178418339Butyllithium

Product 1

HCID 57297643(4S,5S)-4-methyl5-Phenyl-3-(2-methoxyphenylacetyl)-2-oxazolidinoneYield 74.1%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-30 °C

Procedure

9.38 g of 2-methoxyphenylacetic acid are added to a suspension of 1.89 g of sodium hydride (80% dispersion in vaseline) in 200 cm3 of dry tetrahydrofuran, at room temperature. This suspension is cooled to -30° C. 7.77 cm3 of pivaloyl chloride are added and then a solution, cooled to -78° C., which is obtained by adding 35.27 cm3 of a 1.6M solution of butyllithium in hexane to a solution, cooled to -78° C., of 10 g of (4S,5S)-4-methyl-5-phenyl-2-oxazolidinone in 200 cm3 of dry tetrahydrofuran is finally added. The reaction mixture is stirred for 45 minutes at -30° C. and after re-equilibrating to room temperature, 200 cm3 of a saturated aqueous solution of ammonium chloride are added followed by 500 cm3 of ethyl acetate; after decantation, the organic phase is washed twice with 100 cm3 of water and then twice with 100 cm3 of a saturated aqueous solution of sodium chloride; dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 4.8 cm, height 36 cm), eluting under a nitrogen pressure of 0.6 bar with a cyclohexane and ethyl acetate mixture (85/15 followed by 80/20 by volume) and collecting fractions of 50 cm3. Fractions 14 to 31 are pooled and concentrated to dryness under reduced pressure (2.7 kPa). 13.6 g of (4S,5S)-4-methyl-5-phenyl-3-(2-methoxyphenylacetyl)-2-oxazolidinone are obtained in the form of a yellow oil.

Workup

  1. temperaturea solution, cooled to -78° C.
  2. customwhich is obtained
  3. additionis finally added
  4. washafter decantation, the organic phase is washed twice with 100 cm3 of water
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  7. customThe residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 4.8 cm, height 36 cm)
  8. washeluting under a nitrogen pressure of 0.6 bar with a cyclohexane and ethyl acetate mixture (85/15 followed by 80/20 by volume)
  9. customcollecting fractions of 50 cm3
  10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-3c44f0e1e3b848bab1b17d8ae80c6d43
Source dataset
uspto-grants-1996_04
Patent number
US05508433

Reaction notes

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