56660-99-2

Imidazolium-type room temperature ionic liquids (RTILs) have been used for the Stetter reaction, affording the desired 1,4-dicarbonyl compounds in good yields. Thiazolium salts and Et3N are efficient catalysts for this reaction performed in ionic liquid. The possibility to recycle and reuse the solvent has been demonstrated, although it was not possible to recycle the thiazolium catalyst. This method was used in the total synthesis of haloperidol.

A rapid synthesis of - and bromperidol with specific activity exceeding 10 000 Ci/mmol is described in which a trimethylstannylated analogue of bromperidol is used as a substrate for regiospecific no-carrier-added radiobromination. 4--4-hydroxypiperidino>-4'-fluorobutyrophenone was synthesized by the reaction of (trimethylstannyl)sodium with haloperidol and purified by preparative HPLC.Subsequent radiobromination with no-carrier-added 75Br- or 77Br- and in situ oxidation using H2O2/CH3COOH gave a corrected radiochemical yield of 35percent with a 30-min preparation time.Tissue distribution studies in the rat show a rapid and prolonged uptake into the brain, liver, and kidneys and consistently low blood concentrations that differ quantitatively from previous studies using relatively low specific activity bromperidol.Potential clinical applications for this high specific activity radiobrominated neuroleptic are discussed.

The synthesis of [14C] haloperidol for use in metabolism studies, and the synthesis of [d4]- and [d8] haloperidol for use in bioavailability studies, is described.