Diisopropylethylamine → 4-{5-[4-Methoxymethyl-4-(3-methylbenzyl)-piperidine-1-ylmethyl]imidazol-1-ylmethyl}benzonitrile hydrochloride salt

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Reaction Steps

A solution of 4-(3-methylbenzyl)-4-methoxymethylpiperidine hydrochloride salt (1.57 g, 5.8 mmol), 1-(4-cyanobenzyl)-5-chloromethyl-imidazole hydrochloride salt (1.57 g, 5.8 mmol), and diisopropylethyl-amine (5.1 mL, 29 mmol) in anhydrous acetonitrile (75 mL) was heated at 60° C. overnight. The resultant mixture was concentrated under vacuum, and the residue was partitioned between saturated aqueous sodium bicarbonate and dichloromethane. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 3% methanol in chloroform. Collection and concentration of appropriate fractions provided the title compound as free base. The free base obtained was dissolved in anhydrous diethyl ether (50 mL), cooled to 0° C., and bubbled with anhydrous hydrogen chloride gas for 20 second. The resultant mixture was concentrated, and the residue solid recrystallized from a mixture of methanol and diethyl ether. The white solid precipitated was filtered, and residual solvent was removed under vacuum overnight to provide the title compound.

Provenance & Evidence