Imidazole → 6-{[tert-Butyl(dimethyl)silyl]oxy}hexanoic acid

HRID 1154084Notes

Reaction equation

HRID 1154084 reaction equation
[C:1]1(=[O:8])[O:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].[C:11]([Si:15]([CH3:18])([CH3:17])Cl)([CH3:14])([CH3:13])[CH3:12].N1C=CN=C1.C(=O)([O-])[O-:25].[K+].[K+]>O.CO.O.CN(C)C=O>[Si:15]([O:25][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]([OH:7])=[O:8])([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:18])[CH3:17]

Participants

9

Reactant 5

HCID 795ImidazoleHCID 10401epsilon-CAPROLACTONEHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 28928tert-Butyldimethylsilyl chloride

Product 1

HCID 127173116-{[tert-Butyl(dimethyl)silyl]oxy}hexanoic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 22242641Methanol--water (1/1)Solvent2×

Procedure

A round-bottomed flask equipped with a magnetic stirring bar was charged with 22.8 g (0.2 mol) of ε-caprolactone, 8.8 g (0.22 mol) of sodium hydroxide and 200 ml of methanol-water (4:1). The yellow solution was stirred at room temperature under a nitrogen atmosphere for 24 hours. Methanol-water was removed under reduced pressure. Toluene azeotrope was used to remove water. The resulting solid mass was broken up and ground to a fine powder. This powder was heated with 72.0 g (0.48 mol) of t-butyldimethylchlorosilane, 65.3 g (0.96 mol) of imidazole, and 200 ml of dimethylformamide. The mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours. Water (20 ml) was added to this mixture, stirred for 5 minutes, and was diluted with 800 ml of water. The mixture was extracted with 1 liter of hexane-ether (1:1). The aqueous layer was extracted once more with 1 liter of ether. The combined organic phase was washed with water (×2), brine, and dried over anhydrous magnesium sulfate. Filtration and concentration afforded a light yellow oil. This oil was then stirred in a mixture of 27.6 g (0.2 mol) potassium carbonate and 200 mL of methanol-water (4:1). After 3 hours, methanol was removed under reduced pressure. The concentrate was acidified with cold 10% sodium bisulfate until pH 3-5 and the mixture was extracted ether (2×1 liter). The ether layer was washed with water (×3), brine and dried over anhydrous sodium sulfate. Filtration and concentration afforded the crude product. Column chromatography, using 1 Kg CC-4 silica gel, eluting with Skelly B-EtOAc (10:1), gave a pale yellow oil which solidified in the freezer.

Workup

  1. customA round-bottomed flask equipped with a magnetic stirring bar
  2. customMethanol-water was removed under reduced pressure
  3. customto remove water
  4. stirringThe mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours
  5. stirringstirred for 5 minutes
  6. extractionThe mixture was extracted with 1 liter of hexane-ether (1:1)
  7. extractionThe aqueous layer was extracted once more with 1 liter of ether
  8. washThe combined organic phase was washed with water (×2), brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationFiltration and concentration
  11. customafforded a light yellow oil
  12. waitAfter 3 hours
  13. custommethanol was removed under reduced pressure
  14. extractionthe mixture was extracted ether (2×1 liter)
  15. washThe ether layer was washed with water (×3), brine
  16. dry with materialdried over anhydrous sodium sulfate
  17. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-cc5d11f972a84b008225198e96ccdb6f
Source dataset
uspto-grants-1984_12
Patent number
US04487960

Reaction notes

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