Y-Chloro-4-fluorobutyrophenone

A mixture of 6.6 parts of y-chloro-4-fluorobutyrophenone and 12.5 parts of 1-(2-methoxyphenyl)piperazine, heated for 10 hours at a temperature of 110°C. The reaction mixture is treated with 800 parts of ether and filtered. The ether layer is washed with water, dried over anhydrous potassium carbonate and filtered, whereupon hydrogen chloride gas is introduced into the solution. The precipitate is collected on a filter and dissolved in a mixture of 240 parts of 2-propanol and 80 parts of acetone to yield l-[y-(4-fluorobenzoyl)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride. This monohydrochloride is collected on a filter and dissolved in 240 parts of 2-propanol. Anhydrous, gaseous hydrogen chloride is passed through the solution. On cooling, the l-[y-(4-fluorobenzoyl)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride precipitates. 

A mixture of y-chloro-4 -fluorobutyrophenone and l-(2 -pyridyl)piperazine is heated on an oil bath. The mixture is then boiled in diisopropyl ether and the precipitates is collected and boiled with water and benzene. The benzene layer is treated with activated charcoal, added to the ethereal filtrate, and evaporated to give a residue which is taken up in diisopropyl ether. After cooling an oil is precipitated, which after decantation and drying yields l-[y-(4 -fluorobenzoyl)propyl]-4-(2 -pyridyl)piperazine. 

A mixture of 3.4 parts of y-chloro-4-fluorobutyrophenone, 4 parts of l-(4-piperidyl)-2-benzimidazolinone hydrochloride, 6 parts of sodium carbonate and 0.1 part of potassium iodide in 176 parts of 4-methyl-2-pentanone is stirred and refluxed for 48 hours. The reaction mixture is cooled and 120 parts of water is added. The separated organic layer is dried over magnesium sulfate and the solvent is evaporated to leave an oily residue which is dissolved in dilute hydrochloric acid and boiled. The acidic solution is filtered and cooled at room temperature whereupon there crystallizes from solution l-(l-[y-(4-fluorobenzoyl)propyl] -4-piperidyl)-2-benzimidazolinone hydrochloride hydrate melting at about 134°-142°C. 

To a mixture of 4.1 parts of 4-piperidinopiperidine-4-carboxamide, 6.4 parts of sodium carbonate, and a few crystals of potassium iodide in 100 parts of anhydrous toluene is added dropwise a solution of 5.6 parts of y-chloro-4-fluorobutyrophenone and 40 parts of anhydrous toluene at a temperature of 30°C to 40°C. The mixture is stirred and refluxed for 48 hours. The reaction mixture is cooled and divided between 50 parts of water and 60 parts of chloroform. The combined organic layers - toluene and chloroform - are dried over potassium carbonate, filtered, and evaporated. The oily residue solidifies... 

Pipamperone, I. [4.(4-Fluorophenyl)-4-oxobut-< - 1,4 -bipiperidineJ-4 -carboxamide 1 -[3-(p-fluoro-benzoyl)propyl]-[I,4 -bipiperidine]-4 -carboxamide l -ip-fluorophenyl)-4-(4 -piperidino-4 -carbamoylpiperidino)-l butanone l [7-(4-fluorobenzoyl)propyl] -4-piperidinopiper-idine-4-carboxamide 4 -fluoro-4-(/V-[4-(lV-piperidino)-4-carbamido]piperidino]butyrophenone floropipamide R 3345 Dipiperon Piperonyl Prop tan C1,H30FNjOj mol wt 375,49. C 67.17%, H 8.05%, F 5.06%, N 11.19%, 6 8.52%. Prepn of the dihydrochloride by reaction of y-chloro-4-fluorobutyrophenone and 4-piperidinopiperidine-4-carbox-... 

A solution or dispersion consisting of 20.1 g (0.1 mol) of y-chloro-p-fluorobutyrophenone, 19.8 g (0.2 mol) of 4-methylpiperidine and 0.1 g of potassium iodide in 150 ml toluene is heated in a sealed glass tube for 15 hours at 100°C to 110°C. The potassium iodide and the 4-methylpiperidine hydrochloride formed in the reaction are separated by filtration and the solvent removed from the filtrate by evaporation in vacuum on a steam bath. The residue is distilled and the fraction obtained at 120°C to 125°C and at a pressure lower than 0.1 mm Hg is collected. The base is dissolved in ether and the 4-fluoro-y-(4-methylpiperidino)-butyrophenone precipitated as the hydrochloride. The reaction product is purified by recrystallization in ethanol/ether. 

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