Sodium Bicarbonate → (5R)-3-(3-Fluoro-4-{4-ethyl-3-oxopiperazin-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one

HRID 1108580Notes

Reaction equation

HRID 1108580 reaction equation
C([O:8][C:9]([NH:11][C:12]1[CH:13]=[CH:14][C:15]([N:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH3:26])[C:21](=[O:27])[CH2:20]2)=[C:16]([F:18])[CH:17]=1)=[O:10])C1C=CC=CC=1.C([Li])CCC.[CH2:33](OC(=O)CCC)[C@@H:34]1[O:36][CH2:35]1.C(=O)(O)[O-].[Na+]>C1COCC1.C(OCC)(=O)C.CN1CCCN(C)C1=O>[F:18][C:16]1[CH:17]=[C:12]([N:11]2[CH2:33][C@H:34]([CH2:35][OH:36])[O:8][C:9]2=[O:10])[CH:13]=[CH:14][C:15]=1[N:19]1[CH2:24][CH2:23][N:22]([CH2:25][CH3:26])[C:21](=[O:27])[CH2:20]1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 2724536(2R)-Oxiran-2-ylmethyl butanoateHCID 187839155-Benzyloxycarbonylamino-2-(4-ethyl-3-oxopiperazin-1-yl)fluorobenzeneHCID 178418339Butyllithium

Product 1

HCID 54475989(5R)-3-(3-Fluoro-4-{4-ethyl-3-oxopiperazin-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
-78 °C

Procedure

5-Benzyloxycarbonylamino-2-(4-ethyl-3-oxopiperazin-1-yl)fluorobenzene (3.25 g) was dissolved in dry THF (100 ml) under argon. The solution was cooled to -78° C., and treated with a solution of n-butyllithium (1.6 M in hexane, 6.02 ml), keeping the temperature below -60° C. 1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone (DMPU, 10 ml) was added to the resulting mixture to facilitate stirring, and (R)-glycidylbutyrate (1.29 ml) added. Stirring was continued at -78° C. for 30 minutes, before allowing the temperature to rise to ambient over 16 hours. Sodium bicarbonate solution (50 ml) was added, followed by sufficient ethyl acetate to form two layers. The organic layer was separated, washed twice with water, dried (MgSO4) and evaporated. The residue was chromatographed on silica, using as eluant a gradient increasing in polarity from 0 to 6% methanol in dichloromethane. Relevant fractions were combined and evaporated to give (5R)-3-(3-fluoro-4-{4-ethyl-3-oxopiperazine-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one (990 mg).

Workup

  1. customthe temperature below -60° C
  2. stirringStirring
  3. waitto ambient over 16 hours
  4. customto form two layers
  5. customThe organic layer was separated
  6. washwashed twice with water
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe residue was chromatographed on silica
  10. temperaturea gradient increasing in polarity from 0 to 6% methanol in dichloromethane
  11. customevaporated

Sources & evidence

ORD record
ord-1216a2a2be7b44639fa30c36f3890f52
Source dataset
uspto-grants-2000_05
Patent number
US06069145

Reaction notes

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