2-Hydrazinoethanol → Ethyl 5-amino-1-(2-hydroxyethyl)-1H-pyrazole-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

Ethanol (100 mL) and 2-hydroxyethylhydrazine (75% in water) (125 g) were combined, stirred, and heated to about 70° C. Ethyl (ethoxymethylene)cyanoacetate (200 g, 1.18 mol) and ethanol (100 g) were mixed and added over about 1 hour with stirring at about 80° C. After about 2 hours the reaction was completed to give 5-amino-4-ethoxycarbonyl-1-(2′-hydroxyethyl)-pyrazole (I) as evidenced by thin-layer chromatography (ethyl acetate:methanol 7:2, silica gel). The 4-ethoxycarbonyl group was hydrolyzed to the 4-carboxylic acid group by the addition of a solution of sodium hydroxide (60 g) dissolved in water (120 g), followed by refluxing for 3 hours while ethanol was removed by distillation. The pH of the resulting solution then was adjusted at about 0-25° C. to about 4 by the addition of 32% hydrochloric acid, whereupon the tan/yellow product, 5-amino-4-carboxy-1-(2′-hydroxyethyl)pyrazole (II) began to crystallize. After being cooled and stirred at about 0-50° C. for two hours, the reaction mixture was filtered and the solid was collected for use in the next step without drying. On a dry basis, the weight yield was 145 g, 72% of the theoretical yield based on ethyl (ethoxymethylene)cyanoacetate.

Provenance & Evidence