Hydrochloric Acid → Ethyl 5-hydroxymethyl-2-methoxy-benzimidate hydrochloride

Participants

Reaction Steps

Hydrogen chloride gas was passed through a solution of 5-hydroxymethyl-2-methoxy-benzonitrile (250 mg, 1.226 mmol) in anhydrous ethanol (25 mL) at room temperature. After 2 h, hydrogen chloride gas was stopped and the reaction vessel was sealed. After stirring at room temperature for 12 h, the reaction vessel was cooled to 0° C. and opened. The solvent was evaporated in vacuo to dryness to afford crude ethyl 5-hydroxymethyl-2-methoxy-benzimidate hydrochloride. meso-1,2-Bis-(4-chloro-phenyl)-ethane-1,2-diamine (200 mg, 0.711 mmol), triethylamine (145 μL, 1.422 mmol) and ethanol (10 mL) were added and the resulting mixture was heated at reflux for 12 h. The solvent was removed and the residue was taken up in methylene chloride (2 mL) and sodium bicarbonate solution (2 mL). The product was extracted with methylene chloride (2×30 mL). The organic layers were washed with brine (1×5 mL) and dried over anhydrous sodium sulfate. The solid was then filtered off, and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 0-20% methanol in ethyl acetate to afford 4,5-bis-(4-chloro-phenyl)-2-(5-hydroxymethyl-2-methoxy-phenyl)-4,5-dihydro-1H-imidazole (17 mg, 6%). LR-MS (APCI): 427 [(M+H)+].

Provenance & Evidence