Allyl iodide → (S)-4-benzyl-3-((R)-2-(4-fluoro-3-methylphenoxy)pent-4-enoyl)oxazolidin-2-one

HRID 1361066Notes

Reaction equation

HRID 1361066 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:11]([C@H:18]1[CH2:22][O:21][C:20](=[O:23])[N:19]1[C:24](=[O:35])[CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[C:29]([CH3:34])[CH:28]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[CH2:36](I)[CH:37]=[CH2:38].[NH4+].[Cl-]>C1COCC1>[CH2:11]([C@H:18]1[CH2:22][O:21][C:20](=[O:23])[N:19]1[C:24](=[O:35])[C@H:25]([O:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[C:29]([CH3:34])[CH:28]=1)[CH2:38][CH:37]=[CH2:36])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 11166Allyl iodideHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 59775212(S)-4-Benzyl-3-(2-(4-fluoro-3-methylphenoxy)acetyl)oxazolidin-2-one

Product 1

HCID 59775203(S)-4-benzyl-3-((R)-2-(4-fluoro-3-methylphenoxy)pent-4-enoyl)oxazolidin-2-oneYield 31.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-70 °C

Procedure

To the solution of lithium bis(trimethylsilyl)amide (5.2 mL, 5.2 mmol, 1M in THF) in anhydrous 30 mL THF at −70° C. was slowly added over 15 minutes (S)-4-Benzyl-3-(2-(4-fluoro-3-methylphenoxy)acetyl)oxazolidin-2-one (1.5 g, 4.3 mmol) as a solution in 8.0 mL THF. The reaction mixture was stirred for 30 min at −70° C. and then was slowly added a pre-cooled solution of allyl iodide (2.2 g, 13 mmol) in 8 mL of THF. The resulting mixture was stirred at −70° C. for 1 h and the temperature was slowly raised over a period of 2 h. The mixture was poured into 60 mL saturated NH4Cl and extracted with ethyl acetate (3×40 mL). The combined organic layers were washed with brine (2×30 mL) and dried over Na2SO4. The solvent was removed under reduced pressure and the product isolated by Flash column chromatography eluting with 0% to 50% ethyl acetate/hexane to give 521 mg of the title compound as a light yellow oil.

Workup

  1. stirringThe resulting mixture was stirred at −70° C. for 1 h
  2. temperaturethe temperature was slowly raised over a period of 2 h
  3. extractionextracted with ethyl acetate (3×40 mL)
  4. washThe combined organic layers were washed with brine (2×30 mL)
  5. dry with materialdried over Na2SO4
  6. customThe solvent was removed under reduced pressure
  7. customthe product isolated by Flash column chromatography
  8. washeluting with 0% to 50% ethyl acetate/hexane

Sources & evidence

ORD record
ord-7c32937695a94f74830802312903a7ec
Source dataset
uspto-grants-2011_02
Patent number
US07879911B2

Reaction notes

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