(4R,5S)-(+)-4-Methyl-5-phenyl-2-oxazolidinone → (4R,5S)-4-methyl-3-((2R)-2-methyl-4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone

HRID 327808Notes

Reaction equation

HRID 327808 reaction equation
[CH3:1][C@@H:2]1[C@H:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[O:5][C:4](=[O:13])[NH:3]1.C([Li])CCC.[CH3:19][CH:20]([CH2:24][C:25]([F:28])([F:27])[F:26])[C:21](Cl)=[O:22]>O1CCCC1>[CH3:1][C@@H:2]1[C@H:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[O:5][C:4](=[O:13])[N:3]1[C:21](=[O:22])[C@H:20]([CH3:19])[CH2:24][C:25]([F:28])([F:27])[F:26]

Participants

5

Reactant 3

HCID 2733812(4R,5S)-(+)-4-Methyl-5-phenyl-2-oxazolidinoneHCID 15104473HCID 15104473, compoundHCID 178418339Butyllithium

Product 1

HCID 10087044(4R,5S)-4-methyl-3-((2R)-2-methyl-4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinoneYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of (4R,5S)-(+)-4-methyl-5-phenyl-2-oxazolidinone (3.22 g) and tetrahydrofuran (35 ml) at -70° C., under nitrogen was added 1.625M n-butyllithium (12.31 mL) and the mixture was stirred for 15 min. 2-Methyl-4,4,4-trifluorobutyryl chloride (3.5 g) was added to the reaction mixture which was stirred for 15 min at -70° C. and then at 0° C. for 1 hour. The reaction was quenched with ammonium chloride and extracted with ethyl acetate. The organic phase was washed (saturated NaHCO3, brine) and dried (MgSO4). Evaporation and flash chromatography, eluting with 5:95 then 1:9 ethyl acetate:petroelum ether, afforded the two diastereomeric products. Recrystallization from hexane at 20° C. gave (4R,5S)-4-methyl-3-((2R)-2-methyl-4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone (2.376 g, 42%) as colorless needles; mp 72.5°-73.5° C.; TLC, Rf =0.43, 1:9 ethyl acetate:petroleum ether; MS(CI): 316 (M+H).

Workup

  1. stirringwas stirred for 15 min at -70° C.
  2. waitat 0° C. for 1 hour
  3. customThe reaction was quenched with ammonium chloride
  4. extractionextracted with ethyl acetate
  5. washThe organic phase was washed (saturated NaHCO3, brine)
  6. dry with materialdried (MgSO4)
  7. customEvaporation and flash chromatography
  8. washeluting with 5:95
  9. custom1:9 ethyl acetate:petroelum ether, afforded the two diastereomeric products
  10. customRecrystallization from hexane at 20° C.

Sources & evidence

ORD record
ord-9c039cea28ba47898db1d4c1deb54752
Source dataset
uspto-grants-1993_12
Patent number
US05274118

Reaction notes

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