[3-(Trifluoromethoxy)phenyl]hydrazine → 5-cyclopropyl-3-methyl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazole-4-carboxylic acid ethyl ester

Participants

Reaction Steps

To a solution of intermediate 11A, 2-cyclopropanecarbonyl-3-oxo-butyric acid ethyl ester (2.0 g, 10 mmol) in acetic acid (10 ml), cooled at 5° C., was added a solution of (3-Trifluoromethoxy-phenyl)-hydrazine (2.1 g, 11 mmol) in acetic acid (10 ml). The reaction was allowed to come to room temperature (1 h) after which time the reaction was concentrated, the residue dissolved in DCM, washed with saturated NaHCO3, (Na2SO4) and concentrated. Purification by flash column chromatography (EtOAc:n-heptane 1:9) afforded 5-cyclopropyl-3-methyl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazole-4-carboxylic acid ethyl ester (2.8 g, 77%). Saponification of the ester with NaOH in analogy to intermediate 6 affords the title compound.

Provenance & Evidence