Tetrahydrofuran → 2-(2,4-Difluorophenyl)-1-(3-ethoxyphenyl)-1H-imidazole-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

N-(3-Ethoxyphenyl)-2,4-difluorobenzenecarboximidamide To a solution of 2.2 ml (4.4 mmol) of 2.0 M (in tetrahydrofuran) sodium bis(trimethylsilyl)amide in 10 mL of tetrahydrofuran at ambient temperature was added 0.52 mL (4.0 mmol) of 3-ethoxyaniline and the resulting solution was stirred for 20 min. The reaction mixture was cooled to −78° C. and then was added 0.57 ml (4.0 mmol) of 2,4-difluorobenzonitrile. The resulting mixture was stirred from −78° C. to ambient temperature for 5 hrs and then poured into brine (25 mL) and dichloromethane (50 mL). The organic layer was separated and the aqueous layer was extracted with dichloromethane (25 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Flash chromatography on a Biotage Horizon® system (silica gel, 0 to 50% ethyl acetate in hexanes gradient) gave the title compound as a yellow oil. LC/MS 277.2 (M+1).

Provenance & Evidence