Imidazole → HCID 68593414, compound

HRID 898848Notes

Reaction equation

HRID 898848 reaction equation
N1C=CN=C1.[C:6]([O:10][C:11]([C@:13]1([C:24]([O-:26])=[O:25])[CH2:15][C@:14]1([CH2:22][OH:23])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:12])([CH3:9])([CH3:8])[CH3:7].[Na+].[Si:28](Cl)([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C1(C)C=CC=CC=1.CO.O>[C:6]([O:10][C:11]([C@:13]1([C:24]([OH:26])=[O:25])[CH2:15][C@:14]1([CH2:22][O:23][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:12])([CH3:9])([CH3:7])[CH3:8]

Participants

9

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 28928tert-Butyldimethylsilyl chlorideHCID 86600868HCID 86600868, compound

Product 1

HCID 68593414HCID 68593414, compoundYield 98.4%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

Imidazol (18 g, 0.27 mol) was added to a suspension of sodium (1R*,2S*)-1-t-butoxycarbonyl-2-hydroxymethyl-2-phenyl-cyclopropanecarboxylate (38 g, 0.11 mol) obtained in the above-mentioned Example a) in N,N-dimethylformamide (190 mL) under argon atmosphere at 0° C., and t-butyldimethylsilyl chloride (35 g, 0.24 mol) was further added in 2 portions. After warming to room temperature, the mixture was stirred for 12 hours. Then water (76 mL) and methanol (76 mL) were added to the mixture at 0° C., which was followed by addition of potassium carbonate (30 g, 0.21 mol). After the obtained suspension was stirred for 3 hours at room temperature, toluene (190 mL) was added and the mixture was separated into layers using 10% aqueous citric acid solution (400 mL) while adjusting pH to about 5. The aqueous layer was extracted twice with toluene, and the combined organic layer was sequentially washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, and dried over sodium sulfate. After filtration and evaporation, the product was azeotroped with xylene to remove t-butyldimethylsilanol. The title compound (44 g) was obtained as white crystals. The obtained product was used in the next step without purification.

Workup

  1. customat 0° C.
  2. stirringAfter the obtained suspension was stirred for 3 hours at room temperature
  3. customthe mixture was separated into layers
  4. extractionThe aqueous layer was extracted twice with toluene
  5. washthe combined organic layer was sequentially washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationAfter filtration and evaporation
  8. customthe product was azeotroped with xylene
  9. customto remove t-butyldimethylsilanol

Sources & evidence

ORD record
ord-b47e111a6ddd4a1d96c0ea9625a7d1a9
Source dataset
uspto-grants-2008_04
Patent number
US07351825B2

Reaction notes

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