Imidazole → Ethyl 4-((tert-butyldimethylsilyl)oxy)cyclohexanecarboxylate

HRID 2383294Notes

Reaction equation

HRID 2383294 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8][CH2:7]1)=[O:5])[CH3:2].N1C=CN=C1.[C:18]([Si:22]([CH3:25])([CH3:24])Cl)([CH3:21])([CH3:20])[CH3:19]>C1COCC1.CN(C1C=CN=CC=1)C.C(OCC)(=O)C.[Cl-].[NH4+]>[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH:9]([O:12][Si:22]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:25])[CH3:24])[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

8

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 86973Ethyl 4-hydroxycyclohexanecarboxylate

Product 1

HCID 23144129Ethyl 4-((tert-butyldimethylsilyl)oxy)cyclohexanecarboxylateYield 77%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 4-hydroxycyclohexanecarboxylic acid ethyl ester as a mixture of cis and trans isomers (8.7 g, 50.51 mmol) in THF (300 mL) at 0° C. was added imidazole (4.8 g, 70.72 mmol), DMAP (20 mol %, 1.23 g, 10.10 mmol,) and tert-butyl dimethylchlorosilane (9.1 g, 60.61 mmol). The reaction mixture was warmed to room temperature, stirred overnight, and diluted with ethyl acetate and saturated aqueous ammonium chloride. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine and dried over sodium sulfate. Solvent was removed and the crude oil was filtered through silica gel and solvent removed to give 4-(tert-butyldimethylsilanyloxy)cyclohexanecarboxylic acid ethyl ester (11.1 g, 77%) as a mixture of diastereomers.

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate
  2. washthe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. customSolvent was removed
  5. filtrationthe crude oil was filtered through silica gel and solvent
  6. customremoved

Sources & evidence

ORD record
ord-dc68197fd95c4ad28696ddc6e2257f7c
Source dataset
uspto-grants-2012_09
Patent number
US08263618B2

Reaction notes

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