2-(methoxymethyl)aniline

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

Procedure: 528 g of 21.8% strength Na2 [Fe(CO)4 ] solution (0.6 mol; 1 kg of the solution contains 633 g of water, 218 g of Na2 [Fe(CO)4 ], 108 g of Na2CO3 and 41 g of NaOH) are added dropwise to 101 g (0.6 mol) of o-methoxymethylnitrobenzene (Example 3a) in 1 l of methanol at 20°-30° C. Stirring is carried out for 1 hour at room temperature, after which the reaction mixture is diluted with ether. A brown oil separates out in the reaction vessel. The total reaction mixture is poured onto a silica gel column and is eluted with ether. Thereafter, the ether phase is evaporated, the residue is taken up in methylene chloride and the solution is dried over MgSO4. It is filtered under suction over silica gel and the solvent is then evaporated off under reduced pressure. The residue is purified by column chromatography with hexane and methylene chloride. 83.8 g of o-methoxymethylaniline are obtained as a brown oil, which is directly reacted further. The total reaction mixture is poured onto a silica gel column is eluted with ether Thereafter, the ether phase is evaporated the solution is dried over MgSO4 It is filtered under suction over silica gel the solvent is then evaporated off under reduced pressure The residue is purified by column chromatography with hexane and methylene chloride

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

Procedure: A solution of 1-(methoxymethyl)-2-nitrobenzene (4.30 g, 25.7 mmol) and PtO2 (0.29 g, 1.29 mmol) in MeOH (30 mL) was charged with 1 atmosphere hydrogen and stirred at ambient temperature for 1 hour. Charcoal (5 g) was added and the reaction mixture was stirred for 10 minutes. The solid was removed by filtration and washed with methanol. The filtrate was concentrated under reduced pressure to give 2-(methoxymethyl)aniline (3.42 g, 96.9%) as a solid. the reaction mixture was stirred for 10 minutes The solid was removed by filtration washed with methanol The filtrate was concentrated under reduced pressure

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

Procedure: 2-Methoxymethylaniline (1.0 g, 7.2 mmol) and 3-butyryl-4-chloro-8-methoxyquinoline (1.9 g, 7.2 mmol) were heated together under reflux in 1,4-dioxan (50 ml) for 2 hours. The solvent was evaporated and the residue dissolved in dichloromethane, washed with water, sodium hydrogen carbonate solution and brine, dried and evaporated. Recrystallisation from ethanol-water afforded 3-butyryl-4-(2-methoxymethyl-phenylamino)-8-methoxyquinoline, m.p. 128°-30°. The solvent was evaporated the residue dissolved in dichloromethane washed with water, sodium hydrogen carbonate solution and brine dried evaporated Recrystallisation from ethanol-water

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

Procedure: 2-Methoxymethylaniline (1.0 g, 7.2 mmol) and 3-butyryl-4-chloro-8-methoxyquinoline (1.9 g, 7.2 mmol) were heated together under reflux in 1,4-dioxan (50 ml) for 2 hours. The solvent was evaporated and the residue dissolved in dichloromethane, washed with water, sodium hydrogen carbonate solution and brine, dried and evaporated. Recrystallisation from ethanol-water afforded 3-butyryl-4-(2-methoxymethyl-phenylamino)-8-methoxyquinoline, m.p. 128°-30°. The solvent was evaporated the residue dissolved in dichloromethane washed with water, sodium hydrogen carbonate solution and brine dried evaporated Recrystallisation from ethanol-water

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

Procedure: 528 g of 21.8% strength Na2[Fe(CO)4] solution (0.6 mol; 1 kg of the solution contains 633 g of water, 218 g of Na2[Fe(CO)4], 108 g of Na2CO3 and 41 g of NaOH) are added dropwise to 101 g (0.6 mol) of o-methoxymethylnitrobenzene (Example 3a) in 1 l of methanol at 20-30° C. Stirring is carried out for 1 hour at room temperature, after which the reaction mixture is diluted with ether. A brown oil separates out in the reaction vessel. The total reaction mixture is poured onto a silica gel column and is eluted with ether. Thereafter, the ether phase is evaporated, the residue is taken up in methylene chloride and the solution is dried over MgSO4. It is filtered under suction over silica gel and the solvent is then evaporated off under reduced pressure. The residue is purified by column chromatography with hexane and methylene chloride. 83.8 g of o-methoxymethylaniline are obtained as a brown oil, which is directly reacted further. The total reaction mixture is poured onto a silica gel column is eluted with ether Thereafter, the ether phase is evaporated the solution is dried over MgSO4 It is filtered under suction over silica gel the solvent is then evaporated off under reduced pressure The residue is purified by column chromatography with hexane and methylene chloride

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.86 g (50 m moles) of 2-methoxymethylaniline was dissolved in 50 ml of concentrated hydrochloric acid. The solution was cooled to −10° C. Thereto was dropwise added a solution of sodium nitrite (4.14 g, 60 m moles) dissolved in water (50 ml) while a temperature of −10° C. to 0° C. was being kept. Then, a solution of 44.6 g (235 m moles) of stannous chloride dissolved in concentrated hydrochloric acid (50 ml) was dropwise added at the above temperature in 1 hour. After the completion of the dropwise addition, stirring was conducted with a gradual temperature increase to about 20° C. Then, a 10% aqueous sodium hydroxide solution was dropped to obtain a pH of 14, after which extraction with toluene was conducted. The toluene layer was washed with water and concentrated under reduced pressure using a rotary evaporator to obtain 5.40 g (35.5 m moles) of liquid 2-methoxymethylphenylhydrazine. Yield: 71%. was dropwise added at the above temperature in 1 hour After the completion of the dropwise addition increase to about 20° C to obtain a pH of 14 after which extraction with toluene The toluene layer was washed with water concentrated under reduced pressure a rotary evaporator

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

Procedure: 2-Methoxymethylaniline (0.68 g, 4.96 mmol) was dissolved in dichloromethane (50 ml) and the solution was cooled to −70° C. To the cooled solution a solution of tert-butyl hypochlorite (0.54 g, 4.96 mmol) in dichloromethane (1 ml) was added dropwise and the solution was stirred at −70° C. for 10 minutes. To the obtained reaction solution a solution of 2-methylthiomethyl-4,6-dimethoxypyrimidine (0.893 g, 4.46 mmol) in dichloromethane (5 ml) was added dropwise and the solution was stirred at −70° C. for 30 minutes. To the obtained reaction solution a 28% methanol solution of sodium methoxide (4 ml) was added and the solution was stirred until its temperature reached room temperature. Water was added to the reaction solution and the organic layer was separated. The water layer was further extracted twice with dichloromethane. The organic layer was washed with water and dried. Then dichloromethane was distilled off under reduced pressure and the obtained oily substance was purified by column chromatography using 1:6 mixed solvent of ethyl acetate and hexane as eluent to obtain 2-[(4,6-dimethoxypyrimidin-2-yl)-methylthiomethyl]-6-methoxymethylaniline (0.88 g, yield 53%) as oily substance; was added dropwise the solution was stirred at −70° C. for 30 minutes was added the solution was stirred until its temperature reached room temperature the organic layer was separated The water layer was further extracted twice with dichloromethane The organic layer was washed with water dried Then dichloromethane was distilled off under reduced pressure the obtained oily substance was purified by column chromatography

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.86 g (50 m moles) of 2-methoxymethylaniline was dissolved in 50 ml of concentrated hydrochloric acid. The solution was cooled to −10° C. Thereto was dropwise added a solution of sodium nitrite (4.14 g, 60 m moles) dissolved in water (50 ml) while a temperature of −10° C. to 0° C. was being kept. Then, a solution of 44.6 g (235 m moles) of stannous chloride dissolved in concentrated hydrochloric acid (50 ml) was dropwise added at the above temperature in 1 hour. After the completion of the dropwise addition, stirring was conducted with a gradual temperature increase to about 20° C. Then, a 10% aqueous sodium hydroxide solution was dropped to obtain a pH of 14, after which extraction with toluene was conducted. The toluene layer was washed with water and concentrated under reduced pressure using a rotary evaporator to obtain 5.40 g (35.5 m moles) of liquid 2-methoxymethylphenylhydrazine. Yield: 71%. was dropwise added at the above temperature in 1 hour After the completion of the dropwise addition increase to about 20° C to obtain a pH of 14 after which extraction with toluene The toluene layer was washed with water concentrated under reduced pressure a rotary evaporator

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

Procedure: 528 g of 21.8% strength Na2 [Fe(CO)4 ] solution (0.6 mol; 1 kg of the solution contains 633 g of water, 218 g of Na2 [Fe(CO)4 ], 108 g of Na2CO3 and 41 g of NaOH) are added dropwise to 101 g (0.6 mol) of o-methoxymethylnitrobenzene (Example 3a) in 1 l of methanol at 20°-30° C. Stirring is carried out for 1 hour at room temperature, after which the reaction mixture is diluted with ether. A brown oil separates out in the reaction vessel. The total reaction mixture is poured onto a silica gel column and is eluted with ether. Thereafter, the ether phase is evaporated, the residue is taken up in methylene chloride and the solution is dried over MgSO4. It is filtered under suction over silica gel and the solvent is then evaporated off under reduced pressure. The residue is purified by column chromatography with hexane and methylene chloride. 83.8 g of o-methoxymethylaniline are obtained as a brown oil, which is directly reacted further. The total reaction mixture is poured onto a silica gel column is eluted with ether Thereafter, the ether phase is evaporated the solution is dried over MgSO4 It is filtered under suction over silica gel the solvent is then evaporated off under reduced pressure The residue is purified by column chromatography with hexane and methylene chloride

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

Procedure: A solution of 1-(methoxymethyl)-2-nitrobenzene (4.30 g, 25.7 mmol) and PtO2 (0.29 g, 1.29 mmol) in MeOH (30 mL) was charged with 1 atmosphere hydrogen and stirred at ambient temperature for 1 hour. Charcoal (5 g) was added and the reaction mixture was stirred for 10 minutes. The solid was removed by filtration and washed with methanol. The filtrate was concentrated under reduced pressure to give 2-(methoxymethyl)aniline (3.42 g, 96.9%) as a solid. the reaction mixture was stirred for 10 minutes The solid was removed by filtration washed with methanol The filtrate was concentrated under reduced pressure

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

Procedure: A solution of 1-(methoxymethyl)-2-nitrobenzene (4.30 g, 25.7 mmol) and PtO2 (0.29 g, 1.29 mmol) in MeOH (30 mL) was charged with 1 atmosphere hydrogen and stirred at ambient temperature for 1 hour. Charcoal (5 g) was added and the reaction mixture was stirred for 10 minutes. The solid was removed by filtration and washed with methanol. The filtrate was concentrated under reduced pressure to give 2-(methoxymethyl)aniline (3.42 g, 96.9%) as a solid. the reaction mixture was stirred for 10 minutes The solid was removed by filtration washed with methanol The filtrate was concentrated under reduced pressure

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.86 g (50 m moles) of 2-methoxymethylaniline was dissolved in 50 ml of concentrated hydrochloric acid. The solution was cooled to −10° C. Thereto was dropwise added a solution of sodium nitrite (4.14 g, 60 m moles) dissolved in water (50 ml) while a temperature of −10° C. to 0° C. was being kept. Then, a solution of 44.6 g (235 m moles) of stannous chloride dissolved in concentrated hydrochloric acid (50 ml) was dropwise added at the above temperature in 1 hour. After the completion of the dropwise addition, stirring was conducted with a gradual temperature increase to about 20° C. Then, a 10% aqueous sodium hydroxide solution was dropped to obtain a pH of 14, after which extraction with toluene was conducted. The toluene layer was washed with water and concentrated under reduced pressure using a rotary evaporator to obtain 5.40 g (35.5 m moles) of liquid 2-methoxymethylphenylhydrazine. Yield: 71%. was dropwise added at the above temperature in 1 hour After the completion of the dropwise addition increase to about 20° C to obtain a pH of 14 after which extraction with toluene The toluene layer was washed with water concentrated under reduced pressure a rotary evaporator