Water → 2-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclopropyl-pyrimidine

Participants

Reaction Steps

19.2 g of 2-tert-butyl-4-piperazin-1-yl-6-cyclopropyl-pyrimidine (73.7 mmol) were dissolved in 50 ml of toluene. 14.6 ml of 1-bromo-3-chloropropane (147.4 mmol) and 3.4 g of sodium hydroxide (84.7 mmol) were added, followed by dropwise addition of 0.95 g of tetrabutylammonium bromide (2.95 mmol, dissolved in water). After stirring for 5 h at 60° C. additional 1-bromo-3-chloropropane was added to drive the reaction to completion. The reaction mixture was cooled, water was added and the product extracted 3 times with ethyl acetate. The organic layers were dried over magnesium sulfate, filtered, and the solvent was evaporated. The crude product was purified by chromatography on silica gel using dichloromethane/ethyl acetate (9:1). Fractions containing the product were combined, the solvent was evaporated to yield 15.4 g of the title compound.

Provenance & Evidence