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

HRID 2211404Notes

Reaction equation

HRID 2211404 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% strength 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, finally, a solution, cooled to -78° C., 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-oxazolidin-2-one in 200 cm3 of dry tetrahydrofuran is added. The reaction mixture is stirred at -30° C. for 45 minutes and, after returning to room temperature, 200 cm3 of an aqueous saturated solution of ammonium chloride and then 500 cm3 of ethyl acetate are added; after decanting, the organic phase is washed twice with 100 cm 3 of water and then twice with 100 cm3 of an aqueous saturated solution of sodium chloride, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed over a silica gel column (particle size 0.04-0.06 mm, diameter 4.8 cm, height 36 cm) by eluting under a pressure of 0.6 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (85/15 and then 80/20 by volume) and collecting fractions of 50 cm3. Fractions 14 to 31 are combined and concentrated to dryness under reduced pressure (2.7 kPa). 13.6 g of (4S,5S)-4-methyl-5-phenyl-3-(2-methoxyphenylacetyl)-oxazolidin-2-one are obtained in the form of a yellow oil.

Workup

  1. temperaturefinally, a solution, cooled to -78° C.
  2. customobtained
  3. additionis added
  4. customafter returning to room temperature
  5. customafter decanting
  6. washthe organic phase is washed twice with 100 cm 3 of water
  7. dry with materialtwice with 100 cm3 of an aqueous saturated solution of sodium chloride, dried over magnesium sulphate
  8. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  9. customThe residue is chromatographed over a silica gel column (particle size 0.04-0.06 mm, diameter 4.8 cm, height 36 cm)
  10. washby eluting under a pressure of 0.6 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (85/15
  11. custom80/20 by volume) and collecting fractions of 50 cm3
  12. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-fda5bba12b2b4fc1935c1d563dae200a
Source dataset
uspto-grants-1995_10
Patent number
US05463077

Reaction notes

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