4-methoxy-3-phenylmethoxyaniline

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

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

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

Procedure: N,N-1,3-Diisopropyl carbodiimide (0.40 g, 3.36 mmol) was added to a solution of 1-benzyloxy-2-methoxy-5-aminobenzene (0.771 g, 3.36 mmol), 4-benzyloxy-3-methoxy benzoic acid (0.87 g, 3.36 mmol) and 1-hydroxybenzotriazole (0.454 g, 3.36 mmol) in N,N-dimethylformamide (15 ml) and stirred for 12 hrs. The product was precipitated by diluting with a mixture of ethyl acetate/hexane (1:1) (120 ml). Filtration of the reaction mixture provided 1.12 g of 4-Benzyloxy-3-methoxy-N-(3-benzyloxy-4-methoxyphenyl)benzamide. Yield 69%. The product was precipitated by diluting with a mixture of ethyl acetate/hexane (1:1) (120 ml) Filtration of the reaction mixture

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

Procedure: Sodium dithionite (1.5 g) was added to a solution of 1-benzyloxy-2-methoxy-5-nitrobenzene (2.5 gm) in a mixture of methanol (20 ml)/aqueous ammonia (4 ml). After stirring for 12 hrs at room temperature, the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate (75 ml) and water (50 ml). The ethyl acetate layer was washed with water (25 ml), brine solution (25 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Purification by flash chromatography over silica gel eluting with ethyl acetate/hexane (1:1) provided 0.771 g of 1-Benzyloxy-2-methoxy-5-aminobenzene (Yield=35%). the solvent was removed under reduced pressure The residue was partitioned between ethyl acetate (75 ml) and water (50 ml) The ethyl acetate layer was washed with water (25 ml), brine solution (25 ml) dried over anhydrous magnesium sulfate concentrated under reduced pressure Purification by flash chromatography over silica gel eluting with ethyl acetate/hexane (1:1)

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

Procedure: 3-Hydroxy-4-methoxy-1-nitrobenzene was benzylated by refluxing with benzyl bromide with potassium carbonate as a base in acetone which on reduction with sodium dithionite gave 3-benzyloxy-4-methoxy aniline. 4-Hydroxy-3-methoxy benzoic acid was converted to its methyl ester by refluxing in methanol in presence of an acid. The hydroxyl was benzylated using benzyl bromide and potassium carbonate. The ester was hydrolyzed with sodium hydroxide to provide the acid. The aniline and acid were coupled using N,N-1,3-diisopropylcarbodiimide in presence of 1-hydroxybenzotriazole to provide the amide. Finally the benzyl group was removed by hydrogenation in presence of palladium on carbon.

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

Procedure: Sodium dithionite (2 g) was added to a solution of 3,4-Dibenzyloxy-1-nitro benzene (2.37 gm) in a mixture of methanol (30 ml)/aqueous ammonia (5 ml). After stirring for 12 hrs at room temperature, the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate (75 ml) and water (75 ml). The ethyl acetate layer was washed with water (25 ml), brine solution (25 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Purification by flash chromatography over silica gel eluting with ethyl acetate/hexane (1:1) provided 1.0 g of 1-Benzyloxy-2-methoxy-5-aminobenzene (Yield=47%). the solvent was removed under reduced pressure The residue was partitioned between ethyl acetate (75 ml) and water (75 ml) The ethyl acetate layer was washed with water (25 ml), brine solution (25 ml) dried over anhydrous magnesium sulfate concentrated under reduced pressure Purification by flash chromatography over silica gel eluting with ethyl acetate/hexane (1:1)

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

Procedure: To a solution of 2-(benzyloxy)-1-methoxy-4-nitrobenzene (35.35 g, 136 mmol) in 1:1 ethyl acetate: ethanol (640 mL) at 80° C. is added tin(II) chloride hydrate in portions over 25 minutes. The mixture is heated at this temperature for 5 h. The mixture is allowed to cool to room temperature and stirred for 2 days. The mixture is poured into water (1 L) and neutralized with solid sodium bicarbonate. The mixture is extracted three times with ethyl acetate. The combined organic extracts are washed with water and brine, dried (sodium sulfate), filtered and evaporated to yield the title compound as a dark brown oil. The mixture is heated at this temperature for 5 h The mixture is extracted three times with ethyl acetate The combined organic extracts are washed with water and brine dried (sodium sulfate) filtered evaporated

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

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

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

Procedure: N,N-1,3-Diisopropyl carbodiimide (0.40 g, 3.36 mmol) was added to a solution of 1-benzyloxy-2-methoxy-5-aminobenzene (0.771 g, 3.36 mmol), 4-benzyloxy-3-methoxy benzoic acid (0.87 g, 3.36 mmol) and 1-hydroxybenzotriazole (0.454 g, 3.36 mmol) in N,N-dimethylformamide (15 ml) and stirred for 12 hrs. The product was precipitated by diluting with a mixture of ethyl acetate/hexane (1:1) (120 ml). Filtration of the reaction mixture provided 1.12 g of 4-Benzyloxy-3-methoxy-N-(3-benzyloxy-4-methoxyphenyl)benzamide. Yield 69%. The product was precipitated by diluting with a mixture of ethyl acetate/hexane (1:1) (120 ml) Filtration of the reaction mixture

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

Procedure: Sodium dithionite (1.5 g) was added to a solution of 1-benzyloxy-2-methoxy-5-nitrobenzene (2.5 gm) in a mixture of methanol (20 ml)/aqueous ammonia (4 ml). After stirring for 12 hrs at room temperature, the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate (75 ml) and water (50 ml). The ethyl acetate layer was washed with water (25 ml), brine solution (25 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Purification by flash chromatography over silica gel eluting with ethyl acetate/hexane (1:1) provided 0.771 g of 1-Benzyloxy-2-methoxy-5-aminobenzene (Yield=35%). the solvent was removed under reduced pressure The residue was partitioned between ethyl acetate (75 ml) and water (50 ml) The ethyl acetate layer was washed with water (25 ml), brine solution (25 ml) dried over anhydrous magnesium sulfate concentrated under reduced pressure Purification by flash chromatography over silica gel eluting with ethyl acetate/hexane (1:1)

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

Procedure: 3-Hydroxy-4-methoxy-1-nitrobenzene was benzylated by refluxing with benzyl bromide with potassium carbonate as a base in acetone which on reduction with sodium dithionite gave 3-benzyloxy-4-methoxy aniline. 4-Hydroxy-3-methoxy benzoic acid was converted to its methyl ester by refluxing in methanol in presence of an acid. The hydroxyl was benzylated using benzyl bromide and potassium carbonate. The ester was hydrolyzed with sodium hydroxide to provide the acid. The aniline and acid were coupled using N,N-1,3-diisopropylcarbodiimide in presence of 1-hydroxybenzotriazole to provide the amide. Finally the benzyl group was removed by hydrogenation in presence of palladium on carbon.