1-(4-chloro-1,1-dimethoxybutyl)-4-fluorobenzene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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## The mixture is heated to reflux are added The aqueous layer is separated The resultant oil which forms is extracted into chloroform The solvent is removed under reduced pressure to afford an orange oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4.87 Parts of 4-(4-chlorophenyl)piperidin-4-ol, 1.91 parts of potassium iodide and 25 parts of deionized water is stirred together and gently warmed under a nitrogen atmosphere. Then, 2.75 parts of potassium bicarbonate and 6.17 parts of 1,1-dimethoxy-1-(4-fluorophenyl)-4-chlorobutane is added and the mixture is heated to reflux. After heating for 4.5 hours, the reaction mixture is allowed to cool to room temperature and 55 parts of toluene is added. The aqueous and organic layers are separated, and the aqueous layer discarded. 5.1 Parts of methanol is added to the organic layer. Then, 2.5 parts of concentrated hydrochloric acid is added with vigorous stirring. The resulting precipitate is cooled to about 25° C., filtered, washed twice with 22 parts by volume portions of a 10:9:1 mixture of acetone-toluene-methanol, and twice with 20 parts by volume portions of a 10:1 mixture of acetone-methanol. After air-drying, the product, 4-[4-(4-chlorophenyl)-4-hydroxypiperidino]-4' -fluorobutyrophenone hydrochloride, melts at about 227°-229° C. and is obtained in 80.1% yield. This compound is the hydrochloride salt of the product of Example 1. gently warmed under a nitrogen atmosphere the mixture is heated to reflux After heating for 4.5 hours The aqueous and organic layers are separated 5.1 Parts of methanol is added to the organic layer Then, 2.5 parts of concentrated hydrochloric acid is added with vigorous stirring The resulting precipitate is cooled to about 25° C. filtered washed twice with 22 parts by volume portions of a 10:9:1 mixture of acetone-toluene-methanol twice with 20 parts by volume portions of a 10:1 mixture of acetone-methanol After air-drying

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred slurry of 120.0 parts 4-(4-chlorophenyl)piperidin-4-ol hydrochloride and 40.0 parts of potassium iodide in 500 parts of water is warmed to a temperature of about 35° C. under a nitrogen atmosphere. Then, 70.0 parts of potassium hydroxide is added. After further heating to about 55° C., 138.0 parts of 1,1-dimethoxy-1-(4-fluorophenyl)-4-chlorobutane is added. The temperature is then raised to about 102° C. and heating continued for 3.5 hours. After cooling to about 75° C., 785 parts of toluene is added to the reaction mixture and stirred for about 5 minutes. An additional 320 parts of toluene is added and the water and organic layers separated. 102 Parts of methanol is used to rinse the flask and added to the organic layer to provide a solution of 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4,4-dimethoxybutyl]-piperidin-4-ol. Then, 59 parts of concentrated hydrochloric acid is added to a stirred solution of the organic layer to precipitate a solid. The solid is filtered, rinsed twice with 550 parts by volume portions of a 10:9:1 acetone-toluene-methanol mixture, twice with 400 parts by volume portions of a 10:1 acetone-methanol mixture, and air-dried. The dried solid is then dissolved in 1950 parts of methanol with gentle heating on a steam bath. The resulting solution is filtered and 300 parts by volume of concentrated ammonium hydroxide is added. Heating is continued to reflux and maintained thereat for about 1 hour. Then, 2520 parts of water is added and the slurry stirred at about 75° C. for 1.5 hours. After cooling to about 25° C., the solid is filtered, washed twice with 600 parts by volume portions of a 3:1 mixture of water-methanol, and air-dried. The resulting product, 4-[4-chlorophenyl)-4-hydroxypiperidino]-4'-fluorobutyrophenone, is obtained in 32.5% yield. This product melts at about 148.5° - 150.5° C., and is represented by the following structural formula. ##STR8## The temperature is then raised to about 102° C. heating After cooling to about 75° C. the water and organic layers separated to rinse the flask added to the organic layer