Hydrochloric Acid → Azabuperone

Participants

Reaction Steps

To a heated slurry of 2.90 parts of 1,4-diazabicyclo[4.3.0]nonane, 1.91 parts of potassium iodide, and 25 parts of deionized water is added 1.65 parts potassium hydroxide and 6.17 parts of 1,1-dimethoxy-1-(4-fluorophenyl)-4-chlorobutane under nitrogen. The mixture is heated to reflux and held at that temperature for 4.5 hours. After cooling to room temperature, 18 parts of ethyl ether and a sufficient quantity of concentrated hydrochloric acid to bring the pH of the aqueous phase to about 2 are added. The aqueous layer is separated and basified to pH 12 with 50% sodium hydroxide solution. The resultant oil which forms is extracted into chloroform. The solvent is removed under reduced pressure to afford an orange oil. Chromatography of this oil using silica gel as an adsorbant and mixtures of ethanol (0.5 - 20%) in methylene chloride with 0.25% ammonium hydroxide as eluants affords 4-(1,4-diazabicyclo[4.3.0]non-4-yl)-4'-fluorobutyrophenone as an orange oil, in yield of 49%. This compound is represented by the following structural formula. ##STR18##

Provenance & Evidence