2-[2-(1-methylpiperidin-2-yl)ethyl]aniline

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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 process for preparing 4-methoxy-2'-[2-(1-methyl-2-piperidyl) ethyl]benzanilide (I) as the hydrochloride salt ##STR4## which comprises (a) combining α-picoline and dimethylsulfate to form the picolinium methyl sulfate salt (V) ##STR5## which is then reacted with o-nitrobenzaldehyde to produce 1-(2-nitrophenyl)-2-[2-1-methyl) pyridinium methyl sulfate]-ethanol (IV) ##STR6## (b) dehydrating (IV) by heating in a mixture of acetic acid, acetic anhydride and potassium acetate to yield 2-(2-nitrostyrenyl)-[2-(1-methyl) pyridinium methyl sulfate ] (III); ##STR7## (c) hydrogenating (III) using a platinum catalyst to generate 2-(2-aminophenethyl)-1-methylpiperidine (II); and ##STR8## (d) reacting (II) with anisoyl chloride in an organic solvent selected from the group consisting of acetone, acetonitrile, and a C2-5 alkanol, to obtain encainide hydrochloride directly.

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

実験手順: A process for preparing 4-methoxy-2'-[2-(1-methyl-2-piperidyl) ethyl]benzanilide (I) as the hydrochloride salt ##STR4## which comprises (a) combining α-picoline and dimethylsulfate to form the picolinium methyl sulfate salt (V) ##STR5## which is then reacted with o-nitrobenzaldehyde to produce 1-(2-nitrophenyl)-2-[2-1-methyl) pyridinium methyl sulfate]-ethanol (IV) ##STR6## (b) dehydrating (IV) by heating in a mixture of acetic acid, acetic anhydride and potassium acetate to yield 2-(2-nitrostyrenyl)-[2-(1-methyl) pyridinium methyl sulfate ] (III); ##STR7## (c) hydrogenating (III) using a platinum catalyst to generate 2-(2-aminophenethyl)-1-methylpiperidine (II); and ##STR8## (d) reacting (II) with anisoyl chloride in an organic solvent selected from the group consisting of acetone, acetonitrile, and a C2-5 alkanol, to obtain encainide hydrochloride directly.

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

実験手順: Unpurified 2-(2-aminophenethyl)-1-methylpiperidine (II; 14.3 g, 0.066 moles) was dissolved in 100 mL dry acetone and p-anisoyl chloride (12.1 g, 0.071 mole) was added. The reaction mixture was stirred for 16 hours, cooled to 5o, and filtered. The solid material was washed with 25 mL of cold acetone and dried in vacuo at 25o for 6 hours. The dried solid was recrystallized from isopropanol-methanol to give 15.5 g of encainide hydrochloride, m.p. 183°-185°. filtered The solid material was washed with 25 mL of cold acetone dried in vacuo at 25o for 6 hours The dried solid was recrystallized from isopropanol-methanol

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

実験手順: 2-(2-Nitrostyrenyl)-1-methylpyridinium methyl sulfate (III; 25 g, 0.07 moles) and 10 g of 5% Pt on carbon (50% water wet) in 300 mL of 95% ethanol was put in a 2L Parr hydrogenation flask and hydrogenated at approximately 2 psi of hydrogen for 16 hours. The hydrogenation mixture rapidly turned orange and then slowly became colorless as the organic solid dissolved. Catalyst was removed by filtration and held for subsequent runs. The filtrate was concentrated in vacuo to an oil which was dissolved in 50 mL water and made basic (pH~11) with 50% sodium hydroxide solution. The basic aqueous phase was extracted with 50 and 25 mL portions of methylene chloride, the extracts were combined and dried (anhyd. K2CO3) , filtered and the solid removed in vacuo to yield 14.3 g (92%) of product II as an amber oil. This intermediate diamine oil (cf: U.S. 3,931,195; Example 1) was used directly in the next step of the process. The hydrogenation mixture rapidly turned orange and then slowly became colorless as the organic solid dissolved Catalyst was removed by filtration The filtrate was concentrated in vacuo to an oil which was dissolved in 50 mL water The basic aqueous phase was extracted with 50 and 25 mL portions of methylene chloride dried (anhyd. K2CO3) filtered the solid removed in vacuo

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

実験手順: 2-(2-Nitrostyrenyl)-1-methylpyridinium methyl sulfate (III; 25 g, 0.07 moles) and 10 g of 5% Pt on carbon (50% water wet) in 300 mL of 95% ethanol was put in a 2L Parr hydrogenation flask and hydrogenated at approximately 2 psi of hydrogen for 16 hours. The hydrogenation mixture rapidly turned orange and then slowly became colorless as the organic solid dissolved. Catalyst was removed by filtration and held for subsequent runs. The filtrate was concentrated in vacuo to an oil which was dissolved in 50 mL water and made basic (pH~11) with 50% sodium hydroxide solution. The basic aqueous phase was extracted with 50 and 25 mL portions of methylene chloride, the extracts were combined and dried (anhyd. K2CO3) , filtered and the solid removed in vacuo to yield 14.3 g (92%) of product II as an amber oil. This intermediate diamine oil (cf: U.S. 3,931,195; Example 1) was used directly in the next step of the process. The hydrogenation mixture rapidly turned orange and then slowly became colorless as the organic solid dissolved Catalyst was removed by filtration The filtrate was concentrated in vacuo to an oil which was dissolved in 50 mL water The basic aqueous phase was extracted with 50 and 25 mL portions of methylene chloride dried (anhyd. K2CO3) filtered the solid removed in vacuo