[3-(chloromethyl)phenyl]-piperidin-1-ylmethanone

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of this benzoyl piperidine (2.3 9), the above 4-[(4-fluorophenyl)(4-methylthien-2-yl)methylene]piperidine (3 g) and triethylamine (3 ml) in toluene was boiled under reflux for 5 h. Water was added to the cooled mixture, the layers were separated and the toluene layer was separated, washed with brine, dried over sodium sulphate and evaporated. The resultant oil (5.6 g) was dissolved in dichloromethane and chromatographed on silica. Elution with dichloromethane/ammonium hydroxide (1%) containing increasing amounts of methanol gave fractions that on evaporation gave the title compound (4.36 g). A solution of this compound in ether was treated with with an ethereal solution of hydrogen chloride. The precipitate was collected and dried to give the hydrochloride salt (3.6 g) m.p. 118-142° C. under reflux for 5 h the layers were separated the toluene layer was separated washed with brine dried over sodium sulphate evaporated The resultant oil (5.6 g) was dissolved in dichloromethane chromatographed on silica Elution with dichloromethane/ammonium hydroxide (1%) containing increasing amounts of methanol gave fractions that on evaporation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of this benzoyl piperidine (2.3 9), the above 4-[(4-fluorophenyl)(4-methylthien-2-yl)methylene]piperidine (3 g) and triethylamine (3 ml) in toluene was boiled under reflux for 5 h. Water was added to the cooled mixture, the layers were separated and the toluene layer was separated, washed with brine, dried over sodium sulphate and evaporated. The resultant oil (5.6 g) was dissolved in dichloromethane and chromatographed on silica. Elution with dichloromethane/ammonium hydroxide (1%) containing increasing amounts of methanol gave fractions that on evaporation gave the title compound (4.36 g). A solution of this compound in ether was treated with with an ethereal solution of hydrogen chloride. The precipitate was collected and dried to give the hydrochloride salt (3.6 g) m.p. 118-142° C. under reflux for 5 h the layers were separated the toluene layer was separated washed with brine dried over sodium sulphate evaporated The resultant oil (5.6 g) was dissolved in dichloromethane chromatographed on silica Elution with dichloromethane/ammonium hydroxide (1%) containing increasing amounts of methanol gave fractions that on evaporation

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Chloromethylbenzoyl chloride (1.45 ml) was added to a solution of piperidine (1 ml) in triethylamine (2 ml) and the mixture was stirred under nitrogen at 5° C. for 45 min. Water was added, the product was extracted with dichloromethane and the extract was washed with water, dried over sodium sulphate and evaporated to give 1(3-chloromethylbenzoyl)piperidine (2.32 g) as an oil. the product was extracted with dichloromethane the extract was washed with water dried over sodium sulphate evaporated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To an ice-cooled solution of piperidine (67.6 g, 0.793 mole) in tetrahydrofuran (1 L) was added dropwise a solution of 3-chloromethylbenzoyl chloride (100.0 g, 0.529 mmol). When the addition was complete, the reaction mixture was allowed to warm to ambient temperature and was left to stir overnight. The reaction mixture was poured into a solution of 1N hydrochloric acid. This solution was extracted with diethyl ether. The ether extracts were combined, washed with water, dried (MgSO4), and concentrated to afford 108.7 g (86%) of N-(3-(chloromethyl)benzoyl)piperidine (10) as a pale yellow oil whose 1H NMR in CDCl3 supported the structure. When the addition was left This solution was extracted with diethyl ether washed with water dried (MgSO4) concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of this benzoyl piperidine (2.3 9), the above 4-[(4-fluorophenyl)(4-methylthien-2-yl)methylene]piperidine (3 g) and triethylamine (3 ml) in toluene was boiled under reflux for 5 h. Water was added to the cooled mixture, the layers were separated and the toluene layer was separated, washed with brine, dried over sodium sulphate and evaporated. The resultant oil (5.6 g) was dissolved in dichloromethane and chromatographed on silica. Elution with dichloromethane/ammonium hydroxide (1%) containing increasing amounts of methanol gave fractions that on evaporation gave the title compound (4.36 g). A solution of this compound in ether was treated with with an ethereal solution of hydrogen chloride. The precipitate was collected and dried to give the hydrochloride salt (3.6 g) m.p. 118-142° C. under reflux for 5 h the layers were separated the toluene layer was separated washed with brine dried over sodium sulphate evaporated The resultant oil (5.6 g) was dissolved in dichloromethane chromatographed on silica Elution with dichloromethane/ammonium hydroxide (1%) containing increasing amounts of methanol gave fractions that on evaporation

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Chloromethylbenzoyl chloride (1.45 ml) was added to a solution of piperidine (1 ml) in triethylamine (2 ml) and the mixture was stirred under nitrogen at 5° C. for 45 min. Water was added, the product was extracted with dichloromethane and the extract was washed with water, dried over sodium sulphate and evaporated to give 1(3-chloromethylbenzoyl)piperidine (2.32 g) as an oil. the product was extracted with dichloromethane the extract was washed with water dried over sodium sulphate evaporated