2,4,6-Triisopropylbenzenesulfonyl azide → (4S)-3-[(2S)-2-azido-3-methyl-3-phenylbutanoyl]-4-benzyl-1,3-oxazolidin-2-one

HRID 1865748Notes

Reaction equation

HRID 1865748 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][C:16]([CH3:24])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH3:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[K].CC(C1C=C(C(C)C)C(S([N:42]=[N+:43]=[N-:44])(=O)=O)=C(C(C)C)C=1)C>O1CCCC1.C1(C)C=CC=CC=1>[N:42]([C@@H:15]([C:16]([CH3:17])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH3:24])[C:14]([N:9]1[C@@H:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:12][O:11][C:10]1=[O:13])=[O:25])=[N+:43]=[N-:44]

Participants

6

Reactant 3

HCID 3717072,4,6-Triisopropylbenzenesulfonyl azideHCID 5462222PotassiumHCID 10472250(4S)-4-benzyl-3-(3-methyl-3-phenylbutanoyl)-1,3-oxazolidin-2-one

Product 1

HCID 10407303(4S)-3-[(2S)-2-azido-3-methyl-3-phenylbutanoyl]-4-benzyl-1,3-oxazolidin-2-oneYield 96.9%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (4S)-4-benzyl-3-(3-methyl-3-phenylbutanoyl)-1,3-oxazolidin-2-one (1.0 g, 3.0 mmol, from Reference Example 26) in anhydrous tetrahydrofuran (16 mL) is cooled to −78° C. in a dry-ice/acetone bath while stirring under a nitrogen atmosphere. Potassium hexamethylsilazide (0.5 M solution in toluene, 6.6 mL, 3.3 mmol) is added dropwise to the solution via syringe. After stirring for 1 hour at −78° C., trisyl azide (1.2 g, 3.8 mmol) in tetrahydrofuran (8 mL) is added dropwise. The reaction mixture is stirred for 2-3 minutes at −78° C. and then quenched by the addition of glacial acetic acid (0.8 mL). Stirring is continued for 1 hour at 40° C. The reaction mixture is diluted with brine and diethyl ether. The aqueous phase is extracted thrice with diethyl ether. 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 white/yellow solid. The crude material is purified by flash chromatography (ethyl acetate/hexanes) to afford a clear, straw colored oil (1.1 g, 79%). TOF MS (ES+): (M+H)=379.2

Workup

  1. stirringAfter stirring for 1 hour at −78° C.
  2. stirringThe reaction mixture is stirred for 2-3 minutes at −78° C.
  3. customquenched by the addition of glacial acetic acid (0.8 mL)
  4. stirringStirring
  5. additionThe reaction mixture is diluted with brine and diethyl ether
  6. extractionThe aqueous phase is extracted thrice with diethyl ether
  7. washThe combined extracts are washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride
  8. dry with materialdried over sodium sulfate
  9. customdecanted
  10. concentrationconcentrated under reduced pressure
  11. customto afford a white/yellow solid
  12. customThe crude material is purified by flash chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-2234f2cc1fe84afeb5fbcfb17ef20d5e
Source dataset
uspto-grants-2009_12
Patent number
US07626023B2

Reaction notes

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