Downstream synthetic route of 1-((4-Chlorophenyl)(phenyl)methyl)piperazine

As the paragraph descriping shows that 303-26-4 is playing an increasingly important role.

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.303-26-4,1-((4-Chlorophenyl)(phenyl)methyl)piperazine,as a common compound, the synthetic route is as follows.

A vessel is charged with 250 ml of tetrahydrofurane, 25 ml of methanol and 5.0 ml (60 mmol) concentrated hydrochloric acid (37% by weight). The mixture is cooled to the temperature of 15 0C and under intense stirring, 5.5 g ( 84 mmol) pulverized zinc are added. Subsequently at a temperature between 5 tolO 0C, 12.5 g (25.1 mmol) (R)-(+)-4- (4-chloropheny l)-phenylmethyl-piperazine- 1 -carboxylic acid 2,2,2-trichloroethylester hydrochloride (compound of the Example 6) are added in several portions. The suspension is stirred for one hour at room temperature. At the end of the reaction, the unreacted zinc is filtered off, the filtrate is mixed with 150 ml of water and 150 ml of ethylacetate, the organic layer is separated, washed with aqueous 5 % by weight sodium hydrogen carbonate solution, dried and the solvent is evaporated. The residue is dissolved in 100 ml of ethylacetate and is added dropwise with stirring to 80 ml of 10 g/100 ml hydrochloric acid solution prepared in ethylacetate. The suspension containing the crystalline salt, which starts precipitating almost instantly after the addition, is cooled, the product is filtered off, washed with diethylether and dried.Yield: 7.7 g (85.4 %) white crystals Melting temperature, 198-202 0C.Elemental Analysis {calculated on the basis of the Formula C17H19C1N2.2HC1 (359.7)}:Calculated:C: 56 .76 H: 5 .88 Cl: 29.57 N: 7.79Measured: C: 56. ,45 H: 5 .74 Cl: 29.25 N: 7.61Optical purity (chiral high performance liquid chromatography): 98.7, 303-26-4

As the paragraph descriping shows that 303-26-4 is playing an increasingly important role.

Reference:
Patent; EGIS GYOGYSZERGYAR NYRT.; WO2007/66163; (2007); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics