Imidazole → 4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyloxy-1H-pyrazole

Participants

Reaction Steps

To a solution of 1,2-dihydro-4-[(4-iodophenyl)-methyl]-5-isopropyl-3H-pyrazol-3-one (5 g) and imidazole (1.19 g) in N,N-dimethylformamide (20 mL) was added triisopropylsilyl chloride (3.1 g) at room temperature, and the mixture was stirred for 3 hours. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 4-[(4-iodophenyl)methyl]-5-isopropyl-3-triiso-propylsilyloxy-1H-pyrazole (7.27 g). To a solution of obtained 4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyl-oxy-1H-pyrazole (3 g) in N,N-dimethylformamide (10 mL) was added sodium hydride (55%, 0.33 g) under ice-cooling, and the mixture was stirred for 20 minutes. To the reaction mixture were added a solution of 1-benzoyloxy-3-chloropropane (3.0 g) in N,N-dimethylformamide (10 mL) and potassium iodide (0.25 g) at the same temperature, and the resulting mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1-10/1) to give 1-(3-benzoyloxypropyl)-4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyloxy-1H-pyrazole (2.55 g). This material was dissolved in tetrahydrofuran (3 mL). To the solution was added 4 mol/L hydrochloric acid (1,4-dioxane solution, 10 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, and the resulting mixture was poured into water. The organic layer was separated, and the organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue was added a mixed solvent of n-hexane and ethyl acetate (20/1) (10 mL), and the mixture was stirred at room temperature for 1 hour. The precipitated crystals were collected by filtration, and washed with a mixed solvent of n-hexane and ethyl acetate (20/1) and dried under reduced pressure to give the title compound (0.85 g).

Provenance & Evidence