Methyl iodide → (S)-4-benzyl-3-((S)-2-methyl-5-phenylpentanoyl)oxazolidin-2-one

HRID 59694Notes

Reaction equation

HRID 59694 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:25])[CH2:15][CH2:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:26][Si]([N-][Si](C)(C)C)(C)C.[Li+].IC.OS([O-])(=O)=O.[K+]>C1COCC1>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:25])[C@@H:15]([CH3:26])[CH2:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 516920Potassium bisulfateHCID 2733832Lithium HexamethyldisilazideHCID 10783156(4S)-4-benzyl-3-(5-phenylpentanoyl)-1,3-oxazolidin-2-one

Product 1

HCID 90054465(S)-4-benzyl-3-((S)-2-methyl-5-phenylpentanoyl)oxazolidin-2-oneYield 43.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirring solution consisting of (S)-4-benzyl-3-(5-phenylpentanoyl)oxazolidin-2-one (21ma, 1.24 g, 3.68 mmol) in THF (20 mL) at −78° C. was slowly added lithium bis-(trimethylsilyl)amide solution (4.41 mL, 4.41 mmol, 1 M solution in THF). The reaction mixture was stirred at −78° C. for one hour, after which time iodomethane (0.27 mL, 4.2 mmol) was slowly added. The resulting reaction mixture was allowed to rise to room temperature with stirring overnight. The mixture was acidified with 5% KHSO4 and extracted twice with ethyl acetate. The organic layer was washed twice with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography. Elution with ethyl acetate-heptane (25:75 v/v) afforded the title compound (563 mg, 43.6%) as a clear oil; TLC Rf 0.53 (solvent system: 25:75 v/v ethyl acetate-heptane; MS (ESI+) m/z 352.3 (M+H)+374.2 (M+Na)+.

Workup

  1. customThe resulting reaction mixture
  2. customto rise to room temperature
  3. stirringwith stirring overnight
  4. extractionextracted twice with ethyl acetate
  5. washThe organic layer was washed twice with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by silica gel chromatography
  10. washElution with ethyl acetate-heptane (25:75 v/v)

Sources & evidence

ORD record
ord-c87a7e2636c545b69270249f8e25d012
Source dataset
uspto-grants-2016_09
Patent number
US09440919B2

Reaction notes

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