Acetic Acid → Tert-butyl 2-(2-imidazol-1-ylethoxy)acetate

HRID 870591Notes

Reaction equation

HRID 870591 reaction equation
[H-].[Na+].[N:3]1([CH2:8][CH2:9][OH:10])[CH:7]=[CH:6][N:5]=[CH:4]1.[C:11]([OH:14])(=[O:13])[CH3:12].[C:15](=O)(O)[O-].[Na+].O1[CH2:24][CH2:23][CH2:22]C1>>[N:3]1([CH2:8][CH2:9][O:10][CH2:12][C:11]([O:14][C:23]([CH3:22])([CH3:24])[CH3:15])=[O:13])[CH:7]=[CH:6][N:5]=[CH:4]1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 74168N-(2-Hydroxyethyl)imidazoleHCID 516892Sodium Bicarbonate

Product 1

HCID 86726555Tert-butyl 2-(2-imidazol-1-ylethoxy)acetateYield 21%

Procedure

Add sodium hydride (0.79 g; 1.1 equiv; 19.75 mmoles) slowly to a 0° C. solution of 1H-imidazole-1-ethanol (2.01 g; 1.0 equiv; 17.93 mmoles) in tetrahydrofuran (90 mL). Stir for 1 hour, then add acetic acid, bromo-, 1,1-dimethylethyl ester (4.03 mL; 1.49 equiv; 26.76 mmoles) dropwise at 0° C. Warm the solution to ambient temperature and stir for 3 hours, then add 250 mL saturated aqueous sodium bicarbonate solution. Extract the mixture with dichloromethane (3×150 mL). Wash the combined organic extracts with brine (100 mL), dry over sodium sulfate, filter, and concentrate to afford the crude product. Purify this residue by column chromatography (0 to 20% methanol in dichloromethane) to afford tert-butyl 2-(2-imidazol-1-ylethoxy)acetate (0.85 g; 21%) as a viscous yellow-brown oil: MS (m/z): 227(M+1).

Workup

  1. customdropwise at 0° C
  2. stirringstir for 3 hours
  3. extractionExtract the mixture with dichloromethane (3×150 mL)
  4. washWash the combined organic extracts with brine (100 mL)
  5. dry with materialdry over sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate
  8. customto afford the crude product
  9. customPurify this residue by column chromatography (0 to 20% methanol in dichloromethane)

Sources & evidence

ORD record
ord-bab048354fb94a05a742e88ea8f02da1
Source dataset
uspto-grants-2015_03
Patent number
US08969555B2

Reaction notes

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