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

Participants

Reaction Steps

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.

Provenance & Evidence