Potassium Carbonate → 1-Butoxy-2-[3-(3-piperidinomethylphenoxy)propylamino]-1-cyclobutene-3,4-dione

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-piperidinomethyl phenol (0.876 kg; 4.582 moles), 1-butoxy-2-(3-bromopropylamino)-1-cyclobutene-3,4-dione [prepared in Example 10] (1 kg; 3.446 moles), finely powdered (pulverized) potassium carbonate (0.633 kg; 4.582 moles), tris[2-(2-methoxyethoxy)ethyl]amine (0.234 kg; 0.725 mole) in dichloromethane (17.23L) was stirred at 20° C. for 40 hours. The mixture was washed with 3% aqueous sodium hydroxide (2×3L) and then the organic phase was concentrated to dryness under reduced pressure to an oil. The concentrate was diluted with toluene (10L), washed with water (3×2.5L), then extracted with 3N hydrochloric acid (2×2.5L). The cooled aqueous acidic phase was basified with 30% sodium hydroxide then extracted with dichloromethane (2×2.5L). The organic phase was treated with charcoal, stirred for 15 minutes, dried (over magnesium sulfate), filtered through diatomaceous earth and the pad washed with dichloromethane (3×0.25L). The combined filtrate was concentrated to dryness under reduced pressure to give 1300 g (94% yield) of the title compound as a yellowish oil.

Provenance & Evidence