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

HRID 1108588Notes

Reaction equation

HRID 1108588 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][CH2:26][O:27][CH3:28])[C:21](=[O:29])[CH2:20]2)=[C:16]([F:18])[CH:17]=1)=[O:10])C1C=CC=CC=1.C([Li])CCC.[CH2:35](OC(=O)CCC)[C@@H:36]1[O:38][CH2:37]1.C(=O)(O)[O-].[Na+]>C1COCC1.CN1CCCN(C)C1=O>[F:18][C:16]1[CH:17]=[C:12]([N:11]2[CH2:35][C@H:36]([CH2:37][OH:38])[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][CH2:26][O:27][CH3:28])[C:21](=[O:29])[CH2:20]1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 2724536(2R)-Oxiran-2-ylmethyl butanoateHCID 187839065-Benzyloxycarbonylamino-2-(4-{2-methoxyethyl}-3-oxopiperazin-1-yl)fluorobenzeneHCID 178418339Butyllithium

Product 1

HCID 54548494(5R)-3-(3-fluoro-4-{4-(2-methoxyethyl)-3-oxopiperazin-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one

Reagents, catalysts & solvents 2

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

Conditions

Temperature
-78 °C

Procedure

5-Benzyloxycarbonylamino-2-(4-{2-methoxyethyl}-3-oxopiperazin-1-yl)fluorobenzene (3.2 g) was dissolved in dry THF (100 ml) under argon, cooled to -78° C., and treated with a solution of n-butyllithium (1.6 M in hexane, 5.5 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 (0.93 ml) was added. The mixture was stirred at -78° C. for 30 minutes, before allowing the temperature to rise to ambient over 16 hours. Sodium bicarbonate solution (50 ml) was added, and the whole evaporated to dryness. Organic materials were dissolved from the residue using dichloromethane, and purified by chromatography on silica using as eluant a gradient increasing in polarity from 0 to 10% methanol in dichloromethane. Relevant fractions were combined and evaporated to give (5R)-3-(3-fluoro-4-{4-(2-methoxyethyl)-3-oxopiperazin-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one (1.14 g).

Workup

  1. customthe temperature below -60° C
  2. stirringThe mixture was stirred at -78° C. for 30 minutes
  3. customthe whole evaporated to dryness
  4. dissolutionOrganic materials were dissolved from the residue
  5. custompurified by chromatography on silica using as eluant
  6. temperaturea gradient increasing in polarity from 0 to 10% methanol in dichloromethane
  7. customevaporated

Sources & evidence

ORD record
ord-2be8270c178a47128b65812d3a45b958
Source dataset
uspto-grants-2000_05
Patent number
US06069145

Reaction notes

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