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

HRID 1281178Notes

Reaction equation

[OH:1][CH2:2][CH2:3][NH:4][NH2:5].C(O[CH:9]=[C:10]([C:16]#[N:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])C>C(O)C>[NH2:17][C:16]1[N:4]([CH2:3][CH2:2][OH:1])[N:5]=[CH:9][C:10]=1[C:11]([O:13][CH2:14][CH3:15])=[O:12]

Participants

Conditions

Temperature: 70 °C

Procedure

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.

Workup

additionadded over about 1 hour
stirringwith stirring at about 80° C

Sources & evidence

ORD record: ord-c8a35a930fe941119e3544e2e69d1ef6
Source dataset: uspto-grants-2002_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06452019B1

Reaction notes

Loading…