N-[4-(methoxymethyl)piperidin-4-yl]-N-phenylpropanamide

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

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

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

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

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 20 parts of 1-(2-bromoethyl)-4-nitrobenzene, 21.8 parts of N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide, 14.4 parts of N,N-diethylethanamine and 270 parts of N,N-dimethylacetamide is stirred and heated for 4.50 hours at 70° C. The reaction mixture is cooled to room temperature and poured onto water. The product is extracted with methylbenzene. The extract is washed with water, dried, filtered and evaporated. The oily residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 4% of methanol as eluent. The first fraction is collected and the eluent is evaporated, yielding a first fraction of 14 parts of N-{4-(methoxymethyl)-1-[2-(4-nitrophenyl)ethyl]-4-piperidinyl}-N-phenylpropanamide; mp. 98.7° C The second fraction is collected and the eluent is evaporated. The residue is purified once more by column-chromatography over silica gel using a mixture of trichloromethane and 4% of methanol as eluent. The pure fraction is collected and the eluent is evaporated, yielding a second fraction of 2.8 parts of N-{4-(methoxymethyl)-1-[2-(4-nitrophenyl)ethyl]-4-piperidinyl}-N-phenylpropanamide; mp. 98.7° C. The reaction mixture is cooled to room temperature poured onto water The product is extracted with methylbenzene The extract is washed with water dried filtered evaporated The oily residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 4% of methanol as eluent The first fraction is collected the eluent is evaporated

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

Procedure: A mixture of 6.4 parts of sodium carbonate and 120 parts of 4-methyl-2-pentanone is stirred and refluxed with water-separator. Then there are added 4.1 parts of N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide and 5.5 parts of [2-(1-naphthalenyl)ethyl]4-methylbenzenesulfonate and the whole is stirred and refluxed for 20 hours. The reaction mixture is cooled to room temperature and poured onto water. The organic phase is separated, washed with water, dried, filtered and evaporated. The oily residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 7% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The oily residue solidifies on triturating in hexane. The product is filtered off and crystallized from a small amount of 2,2'-oxybispropane, yielding 2.8 parts (43.4%) of N-{4-(methoxymethyl)-1-[2-(1-naphthalenyl)ethyl]-4-piperidinyl}-N-phenylpropanamide; mp. 109.8° C. the whole is stirred refluxed for 20 hours poured onto water The organic phase is separated washed with water dried filtered evaporated The oily residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 7% of methanol as eluent The pure fractions are collected the eluent is evaporated on triturating in hexane The product is filtered off crystallized from a small amount of 2,2'-oxybispropane

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

Procedure: To a stirred and refluxing mixture of 9.5 parts of sodium carbonate and 240 parts of 4-methyl-2-pentanone are added 8.3 parts of N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide and 9.6 parts of [2-(2-furanyl)ethyl] 4-methylbenzenesulfonate (water-separator). The whole is stirred and refluxed for 21 hours. The reaction mixture is cooled to room temperature and poured onto water. The organic phase is separated, washed with water, dried, filtered and evaporated. The oily residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 7% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The residue is converted into the ethanedioate salt in 2-propanol. The salt is filtered off and crystallized from 2-propanol, yielding 5.4 parts (39.1%) of N-{1-[2-(2-furanyl)ethyl]-4-(methoxymethyl)-4-piperidinyl}-N-phenylpropanamide ethanedioate; mp. 178.6° C. refluxing The whole is stirred refluxed for 21 hours poured onto water The organic phase is separated washed with water dried filtered evaporated The oily residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 7% of methanol as eluent The pure fractions are collected the eluent is evaporated The salt is filtered off crystallized from 2-propanol

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

Procedure: A mixture of 3.6 parts of 2-bromo-1-phenyl-1-propanone, 4.1 parts of N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide, 3.5 parts of N-(1-methylethyl)-2-propanamine and 80 parts of 4-methyl-2-pentanone is stirred and refluxed for 16 hours. The reaction mixture is cooled to room temperature and the precipitate is filtered off. The filtrate is evaporated. The oily residue is purified by column-chromatography over silica gel, using a mixture of trichloromethane and 3% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The oily residue solidifies on triturating in petroleumether. The product is filtered off and crystallized from 2,2'-oxybispropane. It is filtered off again and dried, yielding N-[1-(1-benzoylethyl)-4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide; mp. 123° C. refluxed for 16 hours the precipitate is filtered off The filtrate is evaporated The oily residue is purified by column-chromatography over silica gel a mixture of trichloromethane and 3% of methanol as eluent The pure fractions are collected the eluent is evaporated on triturating in petroleumether The product is filtered off crystallized from 2,2'-oxybispropane It is filtered off again dried

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

Procedure: A mixture of 3.54 parts of α-methylphenethyl alcohol, methanesulfonate ester, 4.1 parts of N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide, 3.97 parts of sodium carbonate and 160 parts of 4-methyl-2-pentanone is stirred and refluxed for 24 hours with water-separator. After cooling, water is added and the product is extracted with trichloromethane. The extract is washed with water, dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of benzene and 10% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The residue is converted into the ethanediolate salt in 2-propanol. The salt is filtered off, washed with 2-propanol and dried, yielding N-[4-(methoxymethyl)-1-(1-methyl-2-phenylethyl)-4-piperidinyl]-N-phenylpropanamide ethanedioate; mp. 196.8° C. After cooling the product is extracted with trichloromethane The extract is washed with water dried filtered evaporated The residue is purified by column-chromatography over silica gel using a mixture of benzene and 10% of methanol as eluent The pure fractions are collected the eluent is evaporated The salt is filtered off washed with 2-propanol dried

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

Procedure: A mixture of 3.1 parts of 2-bromoethylbenzene, 4.1 parts of N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide, 0.1 parts of potassium iodide, 2.4 parts of sodium carbonate and 80 parts of 4-methyl-2-pentanone is stirred and refluxed for 48 hours. The reaction mixture is poured onto water and the whole is shaken thoroughly. The organic phase is separated, washed with water, dried, filtered and evaporated. The oily residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 5% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The oily residue solidifies on triturating in n-hexane. The product is filtered off and dried, yielding N-[4-(methoxymethyl)-1-(2-phenylethyl)-4-piperidinyl]-N-phenylpropanamide; mp. 85° C. refluxed for 48 hours The reaction mixture is poured onto water the whole is shaken thoroughly The organic phase is separated washed with water dried filtered evaporated The oily residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 5% of methanol as eluent The pure fractions are collected the eluent is evaporated on triturating in n-hexane The product is filtered off dried

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

Procedure: A mixture of 52 parts of N-[4-(methoxymethyl)-1-(phenylmethyl)-4-piperidinyl]-N-phenylpropanamide and 200 parts of acetic acid is hydrogenated at normal pressure and at room temperature with 3 parts of palladium-on-charcoal catalyst 10%. After the calculated amount of hydrogen is taken up, the catalyst is filtered off and the filtrate is evaporated. The residue is taken up in water, cooled and alkalized with ammonium hydroxide. The product is extracted with trichloromethane. The extract is washed with water, dried, filtered and evaporated, yielding N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide as an oily residue. the catalyst is filtered off the filtrate is evaporated cooled The product is extracted with trichloromethane The extract is washed with water dried filtered evaporated

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

Procedure: A mixture of 2.55 parts of 1,4-dihydro-1-(2-iodoethyl)-4-methyl-5H-tetrazol-5-one, 3.45 parts of N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide, 2 parts of sodium carbonate, 0.2 parts of potassium iodide and 160 parts of 4-methyl-2-pentanone is stirred and refluxed overnight with water-separator. The reaction mixture is cooled, 100 parts of water are added and the layers are separated. The aqueous phase is extracted with dichloromethane. The combined organic phases are dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (97:3 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is converted into the ethanedioate salt in 2-propanone. The salt is filtered off and crystallized from 2-propanone, yielding 2.1 parts (42%) of N-{1-[2-(4,5-dihydro-4-methyl-5-oxo-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)-4-piperidinyl}-N-phenylpropanamide ethanedioate (1:1); mp. 155.9° C. The reaction mixture is cooled the layers are separated The aqueous phase is extracted with dichloromethane The combined organic phases are dried filtered evaporated The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (97:3 by volume) as eluent The pure fractions are collected the eluent is evaporated The salt is filtered off crystallized from 2-propanone