Water → N-[2-(hydroxymethyl)phenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide

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Reaction Steps

A solution of 34.5 g (0.16 mols) 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carbonyl chloride in 50 ml tetrahydrofuran is added dropwise at room temperature to a solution of 20.0 g (0.16 mols) 2-aminophenylmethanol and 36 ml (0.26 mols) triethylamine in 250 ml tetrahydrofuran. After the exotherm has subsided, the reaction is refluxed for 6 hours, then stirred at room temperature for another 48 hours. The reaction mixture is added to about 250 ml water, extracted with ethyl acetate, washed with 2 N hydrochloric acid gewaschen, dried over magnesium sulfate and concentrated tinder vacuum. Column chromatography (gradient cyclohexane/ethyl acetate) yielded 33.8 g (69% theoretical yield) of N-[2-(hydroxymethyl)phenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide [logP (pH 2.3)=1.55].

Provenance & Evidence