Methyl iodide → HCID 69018728, compound

HRID 133837Notes

Reaction equation

HRID 133837 reaction equation
[CH:1]([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[C:10](=[O:21])[CH2:11][C:12]([CH3:20])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:13])([CH3:3])[CH3:2].[Na].I[CH3:24]>O1CCCC1.O.C(OCC)(=O)C>[CH3:24][C@@H:11]([C:12]([CH3:20])([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[CH3:13])[C:10]([N:5]1[C@@H:4]([CH:1]([CH3:3])[CH3:2])[CH2:8][O:7][C:6]1=[O:9])=[O:21]

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 5360545SodiumHCID 11109017HCID 11109017, compound

Product 1

HCID 69018728HCID 69018728, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of (4S)-4-isopropyl-3-(3-methyl-3-phenylbutanoyl)-1,3-oxazolidin-2-one (0.23 g, 0.79 mmol, from Reference Example 23) in anhydrous tetrahydrofuran (3 mL) is cooled to −78° C. in a dry-ice/acetone bath while stirring under a nitrogen atmosphere. Sodium hexamethylsilazide (1.0 M solution in tetrahydrofuran, 0.95 mL, 0.95 mmol) is added dropwise to the solution via syringe. After stirring for 30 minutes at −78° C., iodomethane (0.25 mL, 4.0 mmol) in tetrahydrofuran (1 mL) is added dropwise. The reaction mixture is stirred overnight (18 hours) while warming to room temperature. The reaction mixture is diluted with water (10 mL) and ethyl acetate (10 mL). The aqueous phase is extracted thrice with ethyl acetate. The combined extracts are washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, dried over sodium sulfate, decanted, and concentrated under reduced pressure to afford a clear yellow oil, which slowly solidified to an amorphous solid under high vacuum. The crude material is purified by flash chromatography (ethyl acetate/hexanes) to afford a crystalline solid (0.17 g, 71%). MS (ES+): (M+H)=303.9

Workup

  1. stirringAfter stirring for 30 minutes at −78° C.
  2. stirringThe reaction mixture is stirred overnight (18 hours)
  3. extractionThe aqueous phase is extracted thrice with ethyl acetate
  4. washThe combined extracts are washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride
  5. dry with materialdried over sodium sulfate
  6. customdecanted
  7. concentrationconcentrated under reduced pressure
  8. customto afford a clear yellow oil, which
  9. customThe crude material is purified by flash chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-076eb4f96d8d425ea0b4fc77e9a0ca91
Source dataset
uspto-grants-2008_06
Patent number
US07390910B2

Reaction notes

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