Sodium Bicarbonate → (4S)-4-(phenylmethyl)-3-(2-phenylpropionyl)-2-oxazolidinone

HRID 368824

Reaction equation

HRID 368824 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[C:19]1([CH:25]([CH3:29])[C:26](Cl)=[O:27])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)(O)[O-].[Na+]>C1COCC1>[C:2]1([CH2:1][C@H:8]2[CH2:12][O:11][C:10](=[O:13])[N:9]2[C:26](=[O:27])[CH:25]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH3:29])[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 2760403Hydratropoyl chlorideHCID 178418339Butyllithium

Product 1

HCID 56980759(4S)-4-(phenylmethyl)-3-(2-phenylpropionyl)-2-oxazolidinone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of (4S)-(-)-4-benzyl-2-oxazolidinone (3.903 g, 22.0 mmol) in THF (23 ml) is cooled at -78° and butyl lithium (1.6M in hexane, 14.7 ml, 23.5 mmol) is added. The mixture is stirred for 50 min and then the portion of 2-phenylpropionic acid chloride (XL) from above, in THF (8 ml) is added dropwise to the mixture. The mixture is stirred for 1 hr at -78° and then allowed to warm to 20-25°. Saturated aqueous sodium bicarbonate solution (100 ml) is added and the phases separated. The aqueous phase is washed with ether and the combined organic phases are then washed several times with saturated aqueous sodium bicarbonate followed by a saline wash. The organic phase is dried over magnesium sulfate and concentrated. The resulting diastereomers are separated on silica gel eluting with ethyl acetate/hexane (7/93) followed by ethyl acetate/hexane (12/88). The appropriate fractions are pooled and concentrated to give (4S)-4-(phenylmethyl)-3-(2-phenylpropionyl)-2-oxazolidinone (XLI, Isomer I, less polar isomer), NMR (CDCl3) 1.55, 2.79, 3.35, 4.09, 4.58, 5.12 and 7.30 δ; and (4S)-4-(phenylmethyl)-3-(2-phenylpropionyl)-2-oxazolidinone (XLII, Isomer II, more polar isomer), NMR (CDCl3) δ 1.52, 2.58, 3.09, 4.08, 4.19, 4.75, 5.11, 6.95 and 7.31 δ.

Workup

  1. temperatureis cooled at -78°
  2. stirringThe mixture is stirred for 1 hr at -78°
  3. temperatureto warm to 20-25°
  4. customthe phases separated
  5. washThe aqueous phase is washed with ether
  6. washthe combined organic phases are then washed several times with saturated aqueous sodium bicarbonate
  7. washwash
  8. dry with materialThe organic phase is dried over magnesium sulfate
  9. concentrationconcentrated
  10. customThe resulting diastereomers are separated on silica gel eluting with ethyl acetate/hexane (7/93)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-80dd2d94767b435f9c957400670879fd
Source dataset
uspto-grants-2000_10
Patent number
US06133446

Linked notes

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