(3-Fluorophenyl)carbamic acid benzyl ester → (R)-3-(3-Fluorophenyl)-5-(hydroxymethyl)oxazolidin-2-one

HRID 2256412Notes

Reaction equation

HRID 2256412 reaction equation
[C:1]([NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=1)(OCC1C=CC=CC=1)=O.C([Li])CCC.[C:24]([O:29][CH2:30][C@@H:31]1[O:33]C1)(=[O:28])CCC>O1CCCC1>[F:18][C:14]1[CH:13]=[C:12]([N:11]2[CH2:1][C@H:30]([CH2:31][OH:33])[O:29][C:24]2=[O:28])[CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 895321(3-Fluorophenyl)carbamic acid benzyl esterHCID 2724536(2R)-Oxiran-2-ylmethyl butanoateHCID 178418339Butyllithium

Product 1

HCID 11229590(R)-3-(3-Fluorophenyl)-5-(hydroxymethyl)oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of N-(carbobenzyloxy)-3-fluoroaniline (1.000 g, 4.08 mmol) in dry tetrahydrofuran (10 ml) is cooled with a dry ice/acetone bath to about -78° and then n-butyllithium (1.87 ml of a 1.6M mixture in hexanes, 2.91 mmol) is added. (R)-glycidyl butyrate (0.420 g or 0.413 ml, 2.91 mmol) is then added via syringe and the cooling bath allowed to dissipate overnight, with the reaction mixture reaching 20°-25°. The reaction mixture is quenched by the careful addition of saturated aqueous ammonium chloride, the entire mixture transferred to a separatory funnel with dichloromethane washings, and the mixture extracted with dichloromethane. The combined organic extracts are dried over sodium sulfate, filtered and concentrated under reduced pressure to give a concentrate which is purified by chromatography over silica gel, eluting with acetonitrile/chloroform (10/90) containing 1% methanol, to give the title compound.

Workup

  1. temperatureis cooled with a dry ice/acetone bath to about -78°
  2. customreaching 20°-25°
  3. customThe reaction mixture is quenched by the careful addition of saturated aqueous ammonium chloride
  4. customthe entire mixture transferred to a separatory funnel with dichloromethane washings
  5. extractionthe mixture extracted with dichloromethane
  6. dry with materialThe combined organic extracts are dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give
  10. concentrationa concentrate which
  11. customis purified by chromatography over silica gel
  12. washeluting with acetonitrile/chloroform (10/90)
  13. additioncontaining 1% methanol

Sources & evidence

ORD record
ord-674a47edcaab458eb0ede97bb647336e
Source dataset
uspto-grants-1997_08
Patent number
US05654435

Reaction notes

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