1-(4-fluorophenyl)-4-iodobutan-1-one

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 6.1 g. of 4,4-diphenylpiperidine are heated to boiling with 6.2 g. of 3-(p-fluorobenzoyl)propyl iodide and 5.3 g of anhydrous sodium carbonate in 30 cc. of methyl ethyl ketone for 8 hours while stirring. After cooling, the precipitated salt is filtered off and the filtrate is evaporated to dryness. The residue is dissolved in water and the aqueous solution is rendered alkaline by the addition of sodium hydroxide solution. The resulting base is recovered by repeated extraction with ether. The combined ether extracts are dried over potassium carbonate, the ether is distilled off, and the residue is recrystallized from ethanol with the addition of activated charcoal. Thereby, 9 g. of 1-[3-(p-fluorobenzoyl)propyl] -4,4-diphenylpiperidine of the melting point 107° to 108° C. are obtained. On adding fumaric acid to its solution in ether, the furmarate of the melting point 195° to 197° C. is obtained. After cooling the precipitated salt is filtered off the filtrate is evaporated to dryness The residue is dissolved in water by the addition of sodium hydroxide solution The resulting base is recovered extraction with ether The combined ether extracts are dried over potassium carbonate the ether is distilled off the residue is recrystallized from ethanol with the addition of activated charcoal

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

Procedure: Following the procedure of step F of Example 3, starting from 1-benzyl-4-(methylaminomethyl)piperidine and 1-iodo-3-[(p-fluorophenyl)carbonyl]propane, in the presence of potassium carbonate and in acetone as solvent, the desired compound is obtained in the form of an oil, in a yield of 77%.

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

Procedure: Following the procedure of step F of Example 3, starting from 1-benzyl-4-(methylaminomethyl)piperidine and 1-iodo-3-[(p-fluorophenyl)carbonyl]propane, in the presence of potassium carbonate and in acetone as solvent, the desired compound is obtained in the form of an oil, in a yield of 77%.

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

Procedure: 20 g of 1-chloro-3-(p-fluorophenylcarbonyl)propane dissolved in 100 cm3 of methyl ethyl ketone are refluxed for 24 hours in the presence of 18.5 g of sodium iodide. After treatment, 28 g of the desired compound are isolated.

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

Procedure: 6.1 g. of 4,4-diphenylpiperidine are heated to boiling with 6.2 g. of 3-(p-fluorobenzoyl)propyl iodide and 5.3 g of anhydrous sodium carbonate in 30 cc. of methyl ethyl ketone for 8 hours while stirring. After cooling, the precipitated salt is filtered off and the filtrate is evaporated to dryness. The residue is dissolved in water and the aqueous solution is rendered alkaline by the addition of sodium hydroxide solution. The resulting base is recovered by repeated extraction with ether. The combined ether extracts are dried over potassium carbonate, the ether is distilled off, and the residue is recrystallized from ethanol with the addition of activated charcoal. Thereby, 9 g. of 1-[3-(p-fluorobenzoyl)propyl] -4,4-diphenylpiperidine of the melting point 107° to 108° C. are obtained. On adding fumaric acid to its solution in ether, the furmarate of the melting point 195° to 197° C. is obtained. After cooling the precipitated salt is filtered off the filtrate is evaporated to dryness The residue is dissolved in water by the addition of sodium hydroxide solution The resulting base is recovered extraction with ether The combined ether extracts are dried over potassium carbonate the ether is distilled off the residue is recrystallized from ethanol with the addition of activated charcoal

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

Procedure: 6.1 g. of 4,4-diphenylpiperidine are heated to boiling with 6.2 g. of 3-(p-fluorobenzoyl)propyl iodide and 5.3 g of anhydrous sodium carbonate in 30 cc. of methyl ethyl ketone for 8 hours while stirring. After cooling, the precipitated salt is filtered off and the filtrate is evaporated to dryness. The residue is dissolved in water and the aqueous solution is rendered alkaline by the addition of sodium hydroxide solution. The resulting base is recovered by repeated extraction with ether. The combined ether extracts are dried over potassium carbonate, the ether is distilled off, and the residue is recrystallized from ethanol with the addition of activated charcoal. Thereby, 9 g. of 1-[3-(p-fluorobenzoyl)propyl] -4,4-diphenylpiperidine of the melting point 107° to 108° C. are obtained. On adding fumaric acid to its solution in ether, the furmarate of the melting point 195° to 197° C. is obtained. After cooling the precipitated salt is filtered off the filtrate is evaporated to dryness The residue is dissolved in water by the addition of sodium hydroxide solution The resulting base is recovered extraction with ether The combined ether extracts are dried over potassium carbonate the ether is distilled off the residue is recrystallized from ethanol with the addition of activated charcoal

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

Procedure: A solution of 2.5 g of 1-oxa-4,9-diazaspiro[5.5]undecan-3-one and 5 ml of 4-iodo-p-fluorobutyrophenone in 60 ml of dimethylformamide and 10 ml of triethylamine was heated at 60° C. for 10 hours. The mixture was poured into water, extracted with methylene chloride, and the methylene chloride layer was extracted with aqueous 5% HCl. Basification of the aqueous extract with ammonium hydroxide and extraction with methylene chloride followed by evaporation gave a residue which was crystallized from ethyl acetate-hexane to give 9-[3-(4-fluorobenzoyl)propyl]-1-oxa-4,9-diazaspiro[5.5]undecan-3-one, m.p. 117°-118° C. The HCl salt of 9-[3-(4-fluorobenzoyl)propyl]-1-oxa-4,9-diazaspiro[5.5]undecan-3-one was prepared by dissolving the base in methanolic HCl and precipitating with ether, m.p. 225°-230° C. extracted with methylene chloride the methylene chloride layer was extracted with aqueous 5% HCl Basification of the aqueous extract with ammonium hydroxide and extraction with methylene chloride followed by evaporation gave a residue which was crystallized from ethyl acetate-hexane

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

Procedure: A solution of 2.5 g of 1-oxa-4,9-diazaspiro[5.5]undecan-3-one and 5 ml of 4-iodo-p-fluorobutyrophenone in 60 ml of dimethylformamide and 10 ml of triethylamine was heated at 60° C. for 10 hours. The mixture was poured into water, extracted with methylene chloride, and the methylene chloride layer was extracted with aqueous 5% HCl. Basification of the aqueous extract with ammonium hydroxide and extraction with methylene chloride followed by evaporation gave a residue which was crystallized from ethyl acetate-hexane to give 9-[3-(4-fluorobenzoyl)propyl]-1-oxa-4,9-diazaspiro[5.5]undecan-3-one, m.p. 117°-118° C. The HCl salt of 9-[3-(4-fluorobenzoyl)propyl]-1-oxa-4,9-diazaspiro[5.5]undecan-3-one was prepared by dissolving the base in methanolic HCl and precipitating with ether, m.p. 225°-230° C. extracted with methylene chloride the methylene chloride layer was extracted with aqueous 5% HCl Basification of the aqueous extract with ammonium hydroxide and extraction with methylene chloride followed by evaporation gave a residue which was crystallized from ethyl acetate-hexane

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: When proceeding as described in Example 28, but replacing 3-(p-fluorobenzoyl)propyl iodide (used as the one reactant in said example) by 3-benzoylpropyl iodide and reacting 27.4 g. of said 3-benzoylpropyl iodide with 24.4 g. of 4,4-diphenylpiperidine, on addition of hydrochloric acid to the etheric solution of the diphenylpiperidine base 19.5 g. of 1-(3-benzoylpropyl)-4,4-diphenylpiperidine hydrochloride are obtained. On recrystallization from ethanol, the hydrochloride melts at 200° C.

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

Procedure: When proceeding as described in Example 28, but replacing 3-(p-fluorobenzoyl)propyl iodide (used as the one reactant in said example) by 3-benzoylpropyl iodide and reacting 27.4 g. of said 3-benzoylpropyl iodide with 24.4 g. of 4,4-diphenylpiperidine, on addition of hydrochloric acid to the etheric solution of the diphenylpiperidine base 19.5 g. of 1-(3-benzoylpropyl)-4,4-diphenylpiperidine hydrochloride are obtained. On recrystallization from ethanol, the hydrochloride melts at 200° C.