Sodium Hydroxide → 2-Butyl-5-chloro-1H-imidazole-4-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

31.72 g (250 mmol) of glycine methyl ester hydrochloride was added in a single portion to a solution of 10.13 g (250 mmol) of sodium hydroxide in 80 ml of methanol at 0° C. The temperature dropped to -10° C. The mixture was stirred for 10 minutes, during which time the temperature rose again to 0° C. 108.25 g (a 26.6 percent strength solution in toluene, 250 mmol) of methyl pentanimidate was added, and the mixture was stirred at room temperature for 3 hours. 35.64 g (about 92 percent strength, 275 mmol) of dimethylformamide dimethyl acetal then was added, during the course of 5 minutes. The reaction mixture was stirred for an additional 3 hours. 200 ml of toluene was added, and methanol and water were removed from the mixture by distillation in vacuo. Of the remaining 203.5 g, 91.68 g (corresponding to 112 mmol of methyl pentanimidate) was initially introduced at room temperature and treated with 65.09 g (416 mmol) of POCl3. The mixture was heated 15 100° C. for 1.5 hours and then 118.5 g of POCl3 /toluene was distilled off and the residue was treated with 121 ml of ethyl acetate and 408 ml of water. The pH was adjusted to 1, by addition of 18 ml of 30 percent strength sodium hydroxide solution, and the phases were separated. The aqueous phase was extracted twice, each time with 200 ml of ethyl acetate, and the combined organic-phases were washed with 200 ml of water, dried (MgSO4), and filtered and concentrated. The residue was dried in a high vacuum. 14.07 g of 2-butyl -5-chloroimidazole-4-carbaldehyde (HPLC content 79.9 percent) was obtained. This corresponds to a yield of 56 percent, based on the methyl pentanimidate.

Provenance & Evidence