Hydrochloric Acid → 2-Methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-4-carboxylic acid

HRID 2063272Notes

Reaction equation

HRID 2063272 reaction equation
C[O:2][C:3]([C:5]1[N:6]=[C:7]([CH3:10])[NH:8][CH:9]=1)=[O:4].[H-].[Na+].Cl[CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19].[OH-].[Li+].Cl>CN(C=O)C.O>[CH3:10][C:7]1[N:8]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[CH:9]=[C:5]([C:3]([OH:2])=[O:4])[N:6]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178498881HCID 178498881, compound

Product 1

HCID 582567172-Methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

2-Methyl-1H-imidazole-4-carboxylic acid methyl ester (10.4 g, 74.1 mmol) is taken up in 100 mL DMF, sodium hydride (4.15 g, 60% in mineral oil, 104 mmol) is added portion wise and the reaction mixture is stirred at RT until all gas evolution has ceased. (2-Chloromethoxy-ethyl)-trimethyl-silane (14.4 mL, 81.6 mmol) is added and the reaction mixture is stirred at RT for 0.5 h. Water is added and the reaction mixture is extracted with ethylacetate, the combined organic phases are dried over MgSO4 and concentrated under reduced pressure. The residue (20.0 g) is taken up in 20 mL dioxane and a solution of lithium hydroxide (3.54 g, 148 mmol) in 100 mL water is added slowly. The reaction mixture is stirred overnight at RT. The reaction mixture is cooled to 0° C., acidified to pH 4 by the addition of 6 N hydrochloric acid and extracted with DCM. The combined organic phases are dried over MgSO4 and concentrated under reduced pressure. Yield: 7.01 g. HPLC-MS: tR=2.16 min, (M−H)−=257.

Workup

  1. stirringthe reaction mixture is stirred at RT for 0.5 h
  2. extractionthe reaction mixture is extracted with ethylacetate
  3. dry with materialthe combined organic phases are dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. stirringThe reaction mixture is stirred overnight at RT
  6. temperatureThe reaction mixture is cooled to 0° C.
  7. extractionextracted with DCM
  8. dry with materialThe combined organic phases are dried over MgSO4
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-edd982b9b4b942d088b59730a6a4bf7e
Source dataset
uspto-grants-2012_10
Patent number
US08288379B2

Reaction notes

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