(2R)-Oxiran-2-ylmethyl butanoate → (5R)-3-(3-fluoro-4-{4-methyl-3-oxopiperazin-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one

HRID 1108571Notes

Reaction equation

HRID 1108571 reaction equation
C(O[C:9]([NH:11][C:12]1[CH:13]=[CH:14][C:15]([N:19]2[CH2:24][CH2:23][N:22]([CH3:25])[C:21](=[O:26])[CH2:20]2)=[C:16]([F:18])[CH:17]=1)=O)C1C=CC=CC=1.C([Li])CCC.[CH2:32]([O:36][C:37](=[O:41])CCC)[C@@H:33]1[O:35]C1>C1COCC1>[F:18][C:16]1[CH:17]=[C:12]([N:11]2[CH2:9][C@H:32]([CH2:33][OH:35])[O:36][C:37]2=[O:41])[CH:13]=[CH:14][C:15]=1[N:19]1[CH2:24][CH2:23][N:22]([CH3:25])[C:21](=[O:26])[CH2:20]1

Participants

5

Reactant 3

HCID 2724536(2R)-Oxiran-2-ylmethyl butanoateHCID 187839085-Benzyloxycarbonylamino-2-(4-methyl-3-oxopiperazin-1-yl)fluorobenzeneHCID 178418339Butyllithium

Product 1

HCID 54288185(5R)-3-(3-fluoro-4-{4-methyl-3-oxopiperazin-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

5-Benzyloxycarbonylamino-2-(4-methyl-3-oxopiperazin-1-yl)fluorobenzene (4.5 g) was dissolved in dry THF (100 ml) under argon and the solution cooled to -78° C. A solution of n-butyllithium (8.67 ml, 1.6 M in hexane) was added to this whilst keeping the temperature below -60° C. The mixture was stirred for 5 minutes and (R)-glycidylbutyrate (1.86 ml) was added. Stirring was continued at -78° C. for 30 minutes and the temperature then allowed to rise to ambient over 16 hours. The mixture was evaporated to dryness and then treated with dichloromethane. The mixture was filtered to give (5R)-3-(3-fluoro-4-{4-methyl-3-oxopiperazin-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one (409 mg). The residual organic solution was washed twice with water, and then brine. After drying (MgSO4) and evaporation of solvent, 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 further (5R)-3-(3-fluoro-4-{4-methyl-3-oxopiperazin-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one product (535 mg).

Workup

  1. customthe temperature below -60° C
  2. stirringStirring
  3. waitwas continued at -78° C. for 30 minutes
  4. waitto ambient over 16 hours
  5. customThe mixture was evaporated to dryness
  6. additiontreated with dichloromethane
  7. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-057a30188b17418cb0cb60d582b60c12
Source dataset
uspto-grants-2000_05
Patent number
US06069145

Reaction notes

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