Methylhydrazine → 1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

At −30° C., trifluoroacetyl fluoride (18.3 g, 0.16 mol; 99.5%) was introduced into a solution of methyl 3-piperidin-1-ylacrylate (97%, 25 g, 0.14 mol) and KF (12.5 g, 0.51 mol) in toluene (250 ml). The reaction mixture was stirred at −30° C. for 3 h and then, over a period of one hour, warmed to room temperature. The reaction mixture was washed with deionized water (400 ml). After phase separation, the aqueous phase was extracted once with toluene (200 ml). The toluene phases were combined and, under reduced pressure, concentrated to about 600 ml. The reaction solution obtained in this manner was, at −50° C., added dropwise to a solution of methylhydrazine (7.4 g, 0.16 mol) in toluene (150 ml). The reaction mixture was stirred at −50° C. for 2 h and then, over a period of one hour, warmed to room temperature. Aqueous sodium hydroxide solution (10% strength, 69.4 g, 0.17 mol) was then added, and the reaction mixture was heated under reflux conditions for 2 h. After cooling to room temperature, the phases were separated. The toluene phase was extracted with aqueous sodium hydroxide solution (10% strength, 100 ml). The aqueous phases were combined, adjusted to pH 1 using hydrochloric acid (conc.) and cooled to 0° C. The precipitated solid was filtered off, washed with cyclohexane and, at 60° C., dried under reduced pressure. 3-trifluoromethyl-1-methyl-1H-pyrazol-4-ylcarboxylic acid was obtained in an amount of 21.8 g and a purity of 98% (according to 1H-NMR) (yield: 0.12 mol, 81%).

Provenance & Evidence