3,5-Difluoro-4-methoxybenzaldehyde

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

実験手順: 3,5-Difluoro-4-methoxybenzonitrile (0.237 mol), Raney alloy (40 g) and 90% formic acid (400 ml) were reacted substantially as described in Example 7A above to obtain 22.9 g (56%) of a white, low melting solid. to obtain 22.9 g (56%) of a white, low melting solid

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

実験手順: 3,5-Difluoro-4-methoxybenzonitrile (0.237 mol), Raney alloy (40 g) and 90% formic acid (400 ml) were reacted substantially as described in Example 7A above to obtain 22.9 g (56%) of a white, low melting solid. to obtain 22.9 g (56%) of a white, low melting solid

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3,5-Difluoro-4-methoxybenzaldehyde (3.38 g, 0.0196 mole) was added to aminoacetaldehyde dimethyl acetal (2.14 ml, 0.0196 mole) and the mixture was heated at 100° C. for 2 hours. The reaction mixture was cooled in ice, diluted with ethyl alcohol (35 ml), and sodium borohydride (0.743 g., 0.0196 mole) was added and the mixture was stirred overnight at 25° C. The solvent was removed under reduced pressure, the residue was dissolved in ethyl acetate, and the solution was washed with water and brine and then dried with sodium sulfate. The mixture was filtered, and the solvent removed under reduced pressure to give N-(3,5-difluoro-4-methoxybenzyl)-aminoacetaldehyde dimethyl acetal as an oil (4.94 g, 96%). The reaction mixture was cooled in ice was added The solvent was removed under reduced pressure the residue was dissolved in ethyl acetate the solution was washed with water and brine dried with sodium sulfate The mixture was filtered the solvent removed under reduced pressure

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3,5-Difluoro-4-methoxybenzaldehyde (3.38 g, 0.0196 mole) was added to aminoacetaldehyde dimethyl acetal (2.14 ml, 0.0196 mole) and the mixture was heated at 100° C. for 2 hours. The reaction mixture was cooled in ice, diluted with ethyl alcohol (35 ml), and sodium borohydride (0.743 g., 0.0196 mole) was added and the mixture was stirred overnight at 25° C. The solvent was removed under reduced pressure, the residue was dissolved in ethyl acetate, and the solution was washed with water and brine and then dried with sodium sulfate. The mixture was filtered, and the solvent removed under reduced pressure to give N-(3,5-difluoro-4-methoxybenzyl)-aminoacetaldehyde dimethyl acetal as an oil (4.94 g, 96%). The reaction mixture was cooled in ice was added The solvent was removed under reduced pressure the residue was dissolved in ethyl acetate the solution was washed with water and brine dried with sodium sulfate The mixture was filtered the solvent removed under reduced pressure

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

実験手順: A mixture of 3,5-difluoro-4-methoxybenzonitrile (3.50 g, 0.0207 mole) and Raney catalyst powder (3.5 g) in 90% formic acid (35 ml) was stirred and heated under reflux for 2.5 hours and the catalyst was filtered and washed with hot water and hexane. The hexane layer was separated and the aqueous solution was extracted an additional three times with hexane. The combined hexane extracts were washed with water and brine, dried and the solvent was removed to give 3,5-difluoro-4-methoxybenzaldehyde as an oil (3.38 g, 95%). heated under reflux for 2.5 hours the catalyst was filtered washed with hot water and hexane The hexane layer was separated the aqueous solution was extracted an additional three times with hexane The combined hexane extracts were washed with water and brine dried the solvent was removed

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

実験手順: 3,5-Difluoro-4-methoxybenzonitrile (0.237 mol), Raney alloy (40 g) and 90% formic acid (400 ml) were reacted substantially as described in Example 7A above to obtain 22.9 g (56%) of a white, low melting solid. to obtain 22.9 g (56%) of a white, low melting solid

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-methoxy-3,5-difluorobenzaldehyde (17.2 g, 0.1 mol), aminoacetaldehyde dimethyl acetal (10.5 g, 0.1 mol), and methanol (1 ml) was heated at 95° C. for 10 minutes. The resulting mixture was dissolved in ethanol (150 ml) and hydrogenated over 10% Pd on carbon (1 g) until H2 uptake slowed (about 2 hours). The catalyst was filtered and the filtrate was treated with 1.5N hydrochloric acid (80 ml) and potassium thiocyanate (10.4 g, 0.11 mol). The resulting mixture was boiled until the volume was reduced to 100 ml, then it was heated a reflux an additional 1 hour and cooled to 5° C. The crystalline precipitate was filtered, washed with water, and dried. Recrystallization from ethanol gave 1-(4'-methoxy-3',5'-difluorobenzyl)-1,3-dihydro-2H-imidazole-2-thione, 72% yield, m.p. 156°-158° C. (about 2 hours) The catalyst was filtered it was heated a reflux an additional 1 hour cooled to 5° C The crystalline precipitate was filtered washed with water dried Recrystallization from ethanol

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

実験手順: 3,5-Difluoro-4-methoxybenzonitrile (0.237 mol), Raney alloy (40 g) and 90% formic acid (400 ml) were reacted substantially as described in Example 7A above to obtain 22.9 g (56%) of a white, low melting solid. to obtain 22.9 g (56%) of a white, low melting solid

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3,5-Difluoro-4-methoxybenzaldehyde (3.38 g, 0.0196 mole) was added to aminoacetaldehyde dimethyl acetal (2.14 ml, 0.0196 mole) and the mixture was heated at 100° C. for 2 hours. The reaction mixture was cooled in ice, diluted with ethyl alcohol (35 ml), and sodium borohydride (0.743 g., 0.0196 mole) was added and the mixture was stirred overnight at 25° C. The solvent was removed under reduced pressure, the residue was dissolved in ethyl acetate, and the solution was washed with water and brine and then dried with sodium sulfate. The mixture was filtered, and the solvent removed under reduced pressure to give N-(3,5-difluoro-4-methoxybenzyl)-aminoacetaldehyde dimethyl acetal as an oil (4.94 g, 96%). The reaction mixture was cooled in ice was added The solvent was removed under reduced pressure the residue was dissolved in ethyl acetate the solution was washed with water and brine dried with sodium sulfate The mixture was filtered the solvent removed under reduced pressure

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

実験手順: A mixture of 3,5-difluoro-4-methoxybenzonitrile (3.50 g, 0.0207 mole) and Raney catalyst powder (3.5 g) in 90% formic acid (35 ml) was stirred and heated under reflux for 2.5 hours and the catalyst was filtered and washed with hot water and hexane. The hexane layer was separated and the aqueous solution was extracted an additional three times with hexane. The combined hexane extracts were washed with water and brine, dried and the solvent was removed to give 3,5-difluoro-4-methoxybenzaldehyde as an oil (3.38 g, 95%). heated under reflux for 2.5 hours the catalyst was filtered washed with hot water and hexane The hexane layer was separated the aqueous solution was extracted an additional three times with hexane The combined hexane extracts were washed with water and brine dried the solvent was removed

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

実験手順: 3,5-Difluoro-4-methoxybenzonitrile (0.237 mol), Raney alloy (40 g) and 90% formic acid (400 ml) were reacted substantially as described in Example 7A above to obtain 22.9 g (56%) of a white, low melting solid. to obtain 22.9 g (56%) of a white, low melting solid