title: Efficient synthesis of deuterium labeled hydroxyzine and aripiprazole.
abstract: Hydroxyzine and aripiprazole are active pharmaceutical ingredients that have been largely acknowledged for their antipsychotic properties. Deuterium labeled isotopes of hydroxyzine and aripiprazole are internal standards that can aid in the further research of non-isotopic forms via quantification analysis using HPLC-MS/MS. The synthesis of hydroxyzine-d8 was accomplished by coupling piperazine-d8 with 4-chlorobenzhydryl chloride followed by the reaction of the first intermediate with 2-(2-chloroethoxy) ethanol to afford 11.7% of hydroxyzine-d8 with 99.5% purity. The synthesis of aripiprazole-d8 was also achieved in two steps. 1,4-Dibromobutane-d8 reacted with 7-hydroxy-3,4-dihydro-2(1H)-quinolinone. The first intermediate was then coupled with 1-(2, 3-dichlorophenyl)piperazine hydrochloride to produce 33.4% of aripiprazole-d8 with 99.93% purity.
authors.affiliation: Sussex Research Laboratories Inc., Ottawa, Ontario, Canada.
authors.forename: Mohit
authors.initials: M
authors.lastname: Vohra
authors.forename: Mahendra
authors.initials: M
authors.lastname: Sandbhor
authors.forename: Andrew
authors.initials: A
authors.lastname: Wozniak
mesh_terms: D000068180:Aripiprazole / Q000737:chemistry*; D003903:Deuterium / Q000737:chemistry*; D006919:Hydroxyzine / Q000737:chemistry*; D007553:Isotope Labeling
chemical_list: D006919:Hydroxyzine; D000068180:Aripiprazole; D003903:Deuterium
keywords: aripiprazole; deuterium label; hydroxyzine; internal standard; synthesis