N,N-dimethyl-2-piperidin-4-ylethanamine;dihydrochloride

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

実験手順: A mixture of 2-bromoethyl 2-methoxyphenyl ether (7.5 g), 4-(2-dimethylaminoethyl)piperidine dihydrochloride (7.44 g), triethylamine (18.1 ml) and DMF (50 ml) was heated on a steam bath for 18 hours. The mixture was poured into ice/water (500 ml) and basified with 2M sodium hydroxide. The product was extracted into dichloromethane to give an oil. The oil was triturated with ether. The ether was decanted off and evaporated to give crude 4-(2-dimethylaminoethyl)-1-[2-(2-methoxyphenoxy)ethyl]piperidine (4.58 g) which was added to glacial acetic acid (17 ml) and 48% hydrobromic acid (57 ml). The mixture was heated on a steam bath for 4 hours and then evaporated to dryness. The residue was dissolved in water, basified with 2M sodium hydroxide solution and extracted with dichloromethane to give an oil. The oil was dissolved in ether and acidified with ethereal hydrogen chloride The precipitate was collected by filtration and recrystallised from propan-2-ol to give 2-{2-[4-(2-dimethylaminoethyl)piperidino]ethoxy}phenol dihydrochloride m.p. 273°-275° C. was heated on a steam bath for 18 hours The product was extracted into dichloromethane to give an oil The oil was triturated with ether The ether was decanted off evaporated to give crude 4-(2-dimethylaminoethyl)-1-[2-(2-methoxyphenoxy)ethyl]piperidine (4.58 g) which The mixture was heated on a steam bath for 4 hours evaporated to dryness The residue was dissolved in water extracted with dichloromethane to give an oil was collected by filtration recrystallised from propan-2-ol

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

実験手順: A mixture of 4-(2-dimethylaminoethyl)piperidine dihydrochloride (7.0 g), 2-bromoethyl 3-chlorophenyl ether (7.2 g), triethylamine (12.75 ml) and DMF (50 ml) was heated on a steam bath for 16 hours then worked up as described in Example 16 to give 1-[2-(3-chlorophenoxy)ethyl]-4-(2-dimethylaminoethyl)piperidine dihydrochloride, m.p. 260°-264° C. was heated on a steam bath for 16 hours

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

実験手順: In a similar manner to Example 16, a mixture of 4-(2-dimethylaminoethyl)piperidine dihydrochloride (5.5 g), 2-bromoethyl 4-fluorophenyl ether (5.26 g), triethylamine (13.4 ml) and DMF (50 ml) was heated on a steam bath for 16 hours to give 4-(2-dimethylaminoethyl)-1-[2-(4-fluorophenoxy)ethyl]piperidine dihydrochloride, m.p. 260°-262° C. was heated on a steam bath for 16 hours

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

実験手順: A mixture of 4-(2-dimethylaminoethyl)piperidine dihydrochloride (7.0 g), 2-bromoethyl 4-methylphenyl ether (6.6 g), triethylamine (12.75 ml) and DMF (50 ml) was heated on a steam bath for 16 hours. The mixture was poured into ice/water (500 ml), basified with 2M sodium hydroxide solution and extracted with dichloromethane. The combined organic extracts were washed with water and then extracted with 2M hydrochloric acid. The combined acidic layers were basified with 2M sodium hydroxide solution and then extracted with dichloromethane to give an oil. The oil was distilled at 120° C. at 0.05 mbar and the distillate was dissolved in ether, acidified with ethereal hydrogen chloride solution and filtered. The solid obtained was washed with ether and recrystallised from absolute ethanol to give 4-(2-dimethylaminoethyl)-1-[2-(4-methylphenoxy)ethyl]piperidine dihydrochloride m.p. 281°-283° C. was heated on a steam bath for 16 hours extracted with dichloromethane The combined organic extracts were washed with water extracted with 2M hydrochloric acid extracted with dichloromethane to give an oil The oil was distilled at 120° C. at 0.05 mbar the distillate was dissolved in ether filtered The solid obtained was washed with ether recrystallised from absolute ethanol

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

実験手順: A mixture of 4-(2-dimethylaminoethyl)piperidine dihydrochloride (7.0 g), 2-bromoethyl 4-methylphenyl ether (6.6 g), triethylamine (12.75 ml) and DMF (50 ml) was heated on a steam bath for 16 hours. The mixture was poured into ice/water (500 ml), basified with 2M sodium hydroxide solution and extracted with dichloromethane. The combined organic extracts were washed with water and then extracted with 2M hydrochloric acid. The combined acidic layers were basified with 2M sodium hydroxide solution and then extracted with dichloromethane to give an oil. The oil was distilled at 120° C. at 0.05 mbar and the distillate was dissolved in ether, acidified with ethereal hydrogen chloride solution and filtered. The solid obtained was washed with ether and recrystallised from absolute ethanol to give 4-(2-dimethylaminoethyl)-1-[2-(4-methylphenoxy)ethyl]piperidine dihydrochloride m.p. 281°-283° C. was heated on a steam bath for 16 hours extracted with dichloromethane The combined organic extracts were washed with water extracted with 2M hydrochloric acid extracted with dichloromethane to give an oil The oil was distilled at 120° C. at 0.05 mbar the distillate was dissolved in ether filtered The solid obtained was washed with ether recrystallised from absolute ethanol

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

実験手順: A mixture of 2-bromoethyl 2-methoxyphenyl ether (7.5 g), 4-(2-dimethylaminoethyl)piperidine dihydrochloride (7.44 g), triethylamine (18.1 ml) and DMF (50 ml) was heated on a steam bath for 18 hours. The mixture was poured into ice/water (500 ml) and basified with 2M sodium hydroxide. The product was extracted into dichloromethane to give an oil. The oil was triturated with ether. The ether was decanted off and evaporated to give crude 4-(2-dimethylaminoethyl)-1-[2-(2-methoxyphenoxy)ethyl]piperidine (4.58 g) which was added to glacial acetic acid (17 ml) and 48% hydrobromic acid (57 ml). The mixture was heated on a steam bath for 4 hours and then evaporated to dryness. The residue was dissolved in water, basified with 2M sodium hydroxide solution and extracted with dichloromethane to give an oil. The oil was dissolved in ether and acidified with ethereal hydrogen chloride The precipitate was collected by filtration and recrystallised from propan-2-ol to give 2-{2-[4-(2-dimethylaminoethyl)piperidino]ethoxy}phenol dihydrochloride m.p. 273°-275° C. was heated on a steam bath for 18 hours The product was extracted into dichloromethane to give an oil The oil was triturated with ether The ether was decanted off evaporated to give crude 4-(2-dimethylaminoethyl)-1-[2-(2-methoxyphenoxy)ethyl]piperidine (4.58 g) which The mixture was heated on a steam bath for 4 hours evaporated to dryness The residue was dissolved in water extracted with dichloromethane to give an oil was collected by filtration recrystallised from propan-2-ol

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

実験手順: A mixture of 4-(2-dimethylaminoethyl)piperidine dihydrochloride (7.0 g), 2-bromoethyl 3-chlorophenyl ether (7.2 g), triethylamine (12.75 ml) and DMF (50 ml) was heated on a steam bath for 16 hours then worked up as described in Example 16 to give 1-[2-(3-chlorophenoxy)ethyl]-4-(2-dimethylaminoethyl)piperidine dihydrochloride, m.p. 260°-264° C. was heated on a steam bath for 16 hours

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

実験手順: In a similar manner to Example 16, a mixture of 4-(2-dimethylaminoethyl)piperidine dihydrochloride (5.5 g), 2-bromoethyl 4-fluorophenyl ether (5.26 g), triethylamine (13.4 ml) and DMF (50 ml) was heated on a steam bath for 16 hours to give 4-(2-dimethylaminoethyl)-1-[2-(4-fluorophenoxy)ethyl]piperidine dihydrochloride, m.p. 260°-262° C. was heated on a steam bath for 16 hours

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

実験手順: A mixture of 4-(2-dimethylaminoethyl)piperidine dihydrochloride (7.0 g), 2-bromoethyl 4-methylphenyl ether (6.6 g), triethylamine (12.75 ml) and DMF (50 ml) was heated on a steam bath for 16 hours. The mixture was poured into ice/water (500 ml), basified with 2M sodium hydroxide solution and extracted with dichloromethane. The combined organic extracts were washed with water and then extracted with 2M hydrochloric acid. The combined acidic layers were basified with 2M sodium hydroxide solution and then extracted with dichloromethane to give an oil. The oil was distilled at 120° C. at 0.05 mbar and the distillate was dissolved in ether, acidified with ethereal hydrogen chloride solution and filtered. The solid obtained was washed with ether and recrystallised from absolute ethanol to give 4-(2-dimethylaminoethyl)-1-[2-(4-methylphenoxy)ethyl]piperidine dihydrochloride m.p. 281°-283° C. was heated on a steam bath for 16 hours extracted with dichloromethane The combined organic extracts were washed with water extracted with 2M hydrochloric acid extracted with dichloromethane to give an oil The oil was distilled at 120° C. at 0.05 mbar the distillate was dissolved in ether filtered The solid obtained was washed with ether recrystallised from absolute ethanol