N-(4-氟苯甲酰)哌啶

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of N-methyl-N-(3-chloropropyl)-1,2-benzisothiazole-3-carboxamide (7.13 g), 1-(4-fluorobenzoyl)piperidine (6.44 g), potassium carbonate (7.33 g), and sodium iodide (300 mg) in dry 1-methyl-2-pyrrolidinone (150 ml) was heated to 120° C., with stirring, under nitrogen. After 24 hrs, the mixture was allowed to cool to room temperature, and the residue was partitioned between ethyl acetate/water. The organic phase was washed with water, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The crude residue was chromatographed twice on silica using 10:90 methanol:ethyl acetate as the eluent. The appropriate fractions were collected and evaporated. The residue was dissolved in ether and hydrogen chloride in ethanol was added. Recrystallized of the precipitate from dichloromethane/ether gave 0.642 g (5.09%) of product, mp 189°-191° C. to cool to room temperature the residue was partitioned between ethyl acetate/water The organic phase was washed with water dried over anhydrous magnesium sulfate filtered the filtrate was concentrated in vacuo The crude residue was chromatographed twice on silica using 10:90 methanol The appropriate fractions were collected evaporated The residue was dissolved in ether hydrogen chloride in ethanol was added Recrystallized of the precipitate from dichloromethane/ether

反应条件: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of N-(2-chloroethyl)-1,2-benzisothiazole-3-carboxamide (3.5 g) and 1-(4-fluorobenzoyl)piperidine (3.63 g) in dry 1-methyl-2-pyrrolidinone (125 ml) was heated with stirring to 180° C., under nitrogen. After 3 hr, the reaction mixture was cooled to room temperature and poured into saturated aqueous sodium carbonate solution. The aqueous phase was extracted with ethyl acetate, and the combined organic extracts were washed with water, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The residue was triturated with ether, and the filtrate was concentrated. The residue was chromatographed on silica using ethyl acetate as the eluent. The appropriate fractions were combined and concentrated. The residue was taken up in ether and hydrogen chloride in ether was added. The precipitate was recrystallized from methanol/dichloromethane/ether to provide 1.21 g (18.1%) of product, mp 188°-190° C. was heated the reaction mixture was cooled to room temperature The aqueous phase was extracted with ethyl acetate the combined organic extracts were washed with water dried over anhydrous magnesium sulfate filtered the filtrate was concentrated in vacuo The residue was triturated with ether the filtrate was concentrated The residue was chromatographed on silica concentrated hydrogen chloride in ether was added The precipitate was recrystallized from methanol/dichloromethane/ether

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of N-methyl-N-(3-chloropropyl)-1,2-benzisothiazole-3-carboxamide (7.13 g), 1-(4-fluorobenzoyl)piperidine (6.44 g), potassium carbonate (7.33 g), and sodium iodide (300 mg) in dry 1-methyl-2-pyrrolidinone (150 ml) was heated to 120° C., with stirring, under nitrogen. After 24 hrs, the mixture was allowed to cool to room temperature and the residue was partitioned between ethyl acetate/water. The organic phase was washed with water, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The crude residue was chromatographed twice on silica using 10:90 methanol:ethyl acetate as the eluent. The appropriate fractions were collected and evaporated. The residue was dissolved in ether and hydrogen chloride in ethanol was added Recrystallized of the precipitate from dichloromethane/ether gave 0.642 g (5.09%) of produ mp 189°-191° C. to cool to room temperature the residue was partitioned between ethyl acetate/water The organic phase was washed with water dried over anhydrous magnesium sulfate filtered the filtrate was concentrated in vacuo The crude residue was chromatographed twice on silica using 10:90 methanol The appropriate fractions were collected evaporated The residue was dissolved in ether hydrogen chloride in ethanol was added Recrystallized of the precipitate from dichloromethane/ether gave 0.642 g (5.09%) of produ mp 189°-191° C.

反应条件: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of N-(2-chloroethyl)-1,2-benzisothiazole-3-carboxamide (3.5 g) and 1-(4-fluorobenzoyl)piperidine (3.63 g) in dry 1-methyl-2-pyrrolidinone (125 ml) was heated with stirring to 180° C., under nitrogen. After 3 hr, the reaction mixture was cooled to room temperature and poured into saturated aqueous sodium carbonate solution. The aqueous phase was extracted with ethyl acetate, and the combined organic extracts were washed with water, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The residue was triturated with ether, and the filtrate was concentrated. The residue was chromatographed on silica using ethyl acetate as the eluent. The appropriate fractions were combined and concentrated. The residue was taken up in ether and hydrogen chloride in ether was added. The precipitate was recrystallized from methanol/dichloromethane/ether to provide 1.21 g (18.1%) of product, mp 188°-190° C. was heated the reaction mixture was cooled to room temperature The aqueous phase was extracted with ethyl acetate the combined organic extracts were washed with water dried over anhydrous magnesium sulfate filtered the filtrate was concentrated in vacuo The residue was triturated with ether the filtrate was concentrated The residue was chromatographed on silica concentrated hydrogen chloride in ether was added The precipitate was recrystallized from methanol/dichloromethane/ether

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of N-methyl-N-(3-chloropropyl)-1,2-benzisothiazole-3-carboxamide (7.13 g), 1-(4-fluorobenzoyl)piperidine (6.44 g), potassium carbonate (7.33 g), and sodium iodide (300 mg) in dry 1-methyl-2-pyrrolidinone (150 ml) was heated to 120° C., with stirring, under nitrogen. After 24 hrs, the mixture was allowed to cool to room temperature, and the residue was partitioned between ethyl acetate/water. The organic phase was washed with water, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The crude residue was chromatographed twice on silica using 10:90 methanol:ethyl acetate as the eluent. The appropriate fractions were collected and evaporated. The residue was dissolved in ether and hydrogen chloride in ethanol was added. Recrystallized of the precipitate from dichloromethane/ether gave 0.642 g (5.09%) of product, mp 189°-191° C. to cool to room temperature the residue was partitioned between ethyl acetate/water The organic phase was washed with water dried over anhydrous magnesium sulfate filtered the filtrate was concentrated in vacuo The crude residue was chromatographed twice on silica using 10:90 methanol The appropriate fractions were collected evaporated The residue was dissolved in ether hydrogen chloride in ethanol was added Recrystallized of the precipitate from dichloromethane/ether

反应条件: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of N-(2-chloroethyl)-1,2-benzisothiazole-3-carboxamide (3.5 g) and 1-(4-fluorobenzoyl)piperidine (3.63 g) in dry 1-methyl-2-pyrrolidinone (125 ml) was heated with stirring to 180° C., under nitrogen. After 3 hr, the reaction mixture was cooled to room temperature and poured into saturated aqueous sodium carbonate solution. The aqueous phase was extracted with ethyl acetate, and the combined organic extracts were washed with water, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The residue was triturated with ether, and the filtrate was concentrated. The residue was chromatographed on silica using ethyl acetate as the eluent. The appropriate fractions were combined and concentrated. The residue was taken up in ether and hydrogen chloride in ether was added. The precipitate was recrystallized from methanol/dichloromethane/ether to provide 1.21 g (18.1%) of product, mp 188°-190° C. was heated the reaction mixture was cooled to room temperature The aqueous phase was extracted with ethyl acetate the combined organic extracts were washed with water dried over anhydrous magnesium sulfate filtered the filtrate was concentrated in vacuo The residue was triturated with ether the filtrate was concentrated The residue was chromatographed on silica concentrated hydrogen chloride in ether was added The precipitate was recrystallized from methanol/dichloromethane/ether