Sodium Carbonate → (4-Isopropyl-piperazin-1-yl)-(4-morpholin-4-ylmethyl-phenyl)-methanone

Participants

Reaction Conditions

Reaction Steps

A 1 L three-necked flask equipped with an air stirrer and thermocouple was charged with 4-(4-morpholinylmethyl)benzoic acid hydrochloride (50 g, 0.194 mol), toluene (400 mL), acetonitrile (100 mL) and 1-hydroxybenzotriazole monohydrate (17.8 g, 0.116 mol). After stirring the resulting off-white slurry at about 20-25° C. for 5 minutes, 1-isopropyl-piperazine (27.4 g, 0.213 mol) was added and the reaction mixture was stirred for 20 minutes. Next, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (44.6 g, 0.233 mol) was added and the reaction mixture was stirred at about 20-25° C. overnight. Water (250 mL) and aqueous saturated sodium carbonate (150 mL) were then added to the stirring suspension and mixed well. The resulting biphasic mixture was allowed to settle. The aqueous phase was discarded and the organic phase was washed with a 50% brine solution (water (150 mL)/brine (150 m L)). The organic phase was dried over anhydrous sodium sulfate, filtered, washed with acetonitrile and concentrated to yield (4-isopropyl-piperazin-1-yl)-(4-morpholin-4-ylmethyl-phenyl)-methanone, as a free base, as a light yellow oil.

Provenance & Evidence