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

HRID 1741913Notes

Reaction equation

HRID 1741913 reaction equation
C([Li])CCC.[CH3:6][C@@H:7]1[C@H:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[O:10][C:9](=[O:18])[NH:8]1.[F:19][C:20]([F:27])([F:26])[CH2:21][CH2:22][C:23](Cl)=[O:24]>CCCCCC.O1CCCC1>[CH3:6][C@@H:7]1[C@H:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[O:10][C:9](=[O:18])[N:8]1[C:23](=[O:24])[CH2:22][CH2:21][C:20]([F:27])([F:26])[F:19]

Participants

6

Reactant 3

HCID 2733812(4R,5S)-(+)-4-Methyl-5-phenyl-2-oxazolidinoneHCID 151044744,4,4-Trifluorobutanoyl chlorideHCID 178418339Butyllithium

Product 1

HCID 11779600(4R,5S)-4-methyl-3-(4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinoneYield 86.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-70 °C

Procedure

A solution of n-butyllithium (2.0 mole) in hexane was added to a stirred solution of (4R,5S)-(+)-4-methyl-5-phenyl-2-oxazolidinone (353 g) in dry tetrahydrofuran (2500 mL) at -78° C. under an inert atmosphere. The solution was stirred at -70° C. for 15 min, then 4,4,4-trifluorobutyryl chloride (320 g) was added over 30 min at -60° C. and the mixture warmed to room temperature and stirred overnight. The mixture was evaporated and the residue was partitioned between diethyl ether and water. The ethereal layer was washed (1N hydrochloric acid, brine (twice)), dried (MgSO4), and evaporated to yield crude product (604 g, about 100%). Filtration through 3000 mL of silica gel using 1:1 methylene chloride:hexanes as the eluent afforded a white solid. Recrystallization from methylene chloride:hexanes afforded (4R,5S)-4-methyl-3-(4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone (519 g, 86%); mp 93°-95° C.; partial NMR (300 MHz, CDCl3): 0.91 (d, 3H, CH3), 2.45-2.65 (m, 2H, CF3CH2), 3.18-3.40 (m, 2H, CH2CO), 4.78 (m, 1H, 4-H oxazolidinone), 5.70 (d, 1H, 5-H oxazolidone), 7.30-7.44 (m, 5H, Ar).

Workup

  1. temperaturethe mixture warmed to room temperature
  2. stirringstirred overnight
  3. customThe mixture was evaporated
  4. customthe residue was partitioned between diethyl ether and water
  5. washThe ethereal layer was washed (1N hydrochloric acid, brine (twice))
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customto yield crude product (604 g, about 100%)
  9. filtrationFiltration through 3000 mL of silica gel using 1:1 methylene chloride
  10. customhexanes as the eluent afforded a white solid
  11. customRecrystallization from methylene chloride

Sources & evidence

ORD record
ord-443bd060c040487d9ce97c2f0ff298fb
Source dataset
uspto-grants-1994_08
Patent number
US05334765

Reaction notes

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