Reaction #4411

Reaction equation

1-phenacylpiperazine

1-chloro-3-[4-(4-chlorobenzyl)-1-piperazinyl]propane

triethylamine

→

1-[4-(4-chlorobenzyl)-1-piperazinyl]-3-(4-phenacyl-1-piperazinyl)propane

Yield 77.5%

Solvents

ethanol

Conditions

Workup

1. 1
   Temperaturewas refluxed for 5 hours
2. 2
   OtherThe solvent was removed by rotary evaporation, 150 ml of water
3. 3
   workup.ADDITIONwere added
4. 4
   Extractionthe mixture was extracted with ether (3×150 ml)
5. 5
   OtherThe ether solution was evaporated to an oil, which
6. 6
   Otherwas chromatographed on a silica column

Procedure

A mixture of 4.1 g of 1-phenacylpiperazine, 5.7 g of 1-chloro-3-[4-(4-chlorobenzyl)-1-piperazinyl]propane, 2.6 g of triethylamine and 35 ml of reagent ethanol was refluxed for 5 hours. The solvent was removed by rotary evaporation, 150 ml of water were added, and the mixture was extracted with ether (3×150 ml). The ether solution was evaporated to an oil, which was chromatographed on a silica column, the eluant being CH2Cl2 /CH3OH/ammonium hydroxide (45:5:1), to yield crude 1-[4-(4-chlorobenzyl)-1-piperazinyl]-3-(4-phenacyl-1-piperazinyl)propane (7.0 g, 50% of theory). This oil was dissolved in 200 ml of ether and precipitated with excess anhydrous hydrogen chloride. The precipitate was then dissolved in water and reprecipitated by addition of acetone to give 1-[4-(4-chlorobenzyl)-1-piperazinyl]-3-(4-phenacyl-1-piperazinyl)propane tetrahydrochloride monohydrate as a white crystalline product (m.p. 211°-218° C.).

Source