methyl 3-amino-5-(hydroxymethyl)benzoate

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

Procedure: Methyl 3-(hydroxymethyl)-5-nitrobenzoate (11.2 g, 53 mmol) in methanol (50 mL) was flushed with nitrogen, and treated with palladium (10% on charcoal, 1.1 g). The flask was flushed with hydrogen and allowed to stir under an atmosphere of hydrogen overnight. The reaction was flushed with nitrogen, filtered through celite, and concentrated. Column chromatography on silica gel (50% ethyl acetate/hexanes) afforded 2.8 g (29%). 1H-NMR (CD3OD, 300 MHz) δ 7.34 (s, 1H), 7.27 (s, 1H), 6.94 (s, 1H), 4.55 (s, 2H), 3.88 (s, 3H). Mass spec.: 182.09 (MH)+. The flask was flushed with hydrogen The reaction was flushed with nitrogen filtered through celite concentrated Column chromatography on silica gel (50% ethyl acetate/hexanes) afforded 2.8 g (29%)

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

Procedure: Methyl 3-(hydroxymethyl)-5-nitrobenzoate (11.2 g, 53 mmol) in methanol (50 mL) was flushed with nitrogen, and treated with palladium (10% on charcoal, 1.1 g). The flask was flushed with hydrogen and allowed to stir under an atmosphere of hydrogen overnight. The reaction was flushed with nitrogen, filtered through celite, and concentrated. Column chromatography on silica gel (50% ethyl acetate/hexanes) afforded 2.8 g (29%). 1H-NMR (CD3OD, 300 MHz) δ 7.34 (s, 1H), 7.27 (s, 1H), 6.94 (s, 1H), 4.55 (s, 2H), 3.88 (s, 3H). Mass spec.: 182.09 (MH)+. The flask was flushed with hydrogen The reaction was flushed with nitrogen filtered through celite concentrated Column chromatography on silica gel (50% ethyl acetate/hexanes) afforded 2.8 g (29%)

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

Procedure: Methyl 3-(hydroxymethyl)-5-nitrobenzoate (11.2 g, 53 mmol) in methanol (50 mL) was flushed with nitrogen, and treated with palladium (10% on charcoal, 1.1 g). The flask was flushed with hydrogen and allowed to stir under an atmosphere of hydrogen overnight. The reaction was flushed with nitrogen, filtered through celite, and concentrated. Column chromatography on silica gel (50% ethyl acetate/hexanes) afforded 2.8 g (29%). 1H-NMR (CD3OD, 300 MHz) δ 7.34 (s, 1H), 7.27 (s, 1H), 6.94 (s, 1H), 4.55 (s, 2H), 3.88 (s, 3H). Mass spec.: 182.09 (MH)+. The flask was flushed with hydrogen The reaction was flushed with nitrogen filtered through celite concentrated Column chromatography on silica gel (50% ethyl acetate/hexanes) afforded 2.8 g (29%)

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

Procedure: 85 g of 3-nitro-5-methoxycarbonylbenzoic acid was dissolved in 200 ml of THF under a flow of nitrogen, and 43.4 ml of borane dimethylsulfide complex was added with stirring under ice-cooling. After stirring for 18 hours, 200 ml of water was added, and then 96 g of potassium carbonate was added. It was extracted with ethyl acetate, and theorganic layer was washed with salt solution. After drying with magnesium sulfate, the resulting solid was dissolved in 800 ml of ethyl acetate, 750 mg of 10% Pd/C was added, and stirring was continued under the flow of hydrogen. After the reaction was completed, it was subjected to the filtration, and then the filtrate was concentrated to produce 64 g of the title compound. was added cooling After stirring for 18 hours It was extracted with ethyl acetate, and theorganic layer was washed with salt solution After drying with magnesium sulfate the resulting solid was dissolved in 800 ml of ethyl acetate 750 mg of 10% Pd/C was added stirring it was subjected to the filtration the filtrate was concentrated

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

Procedure: 85 g of 3-nitro-5-methoxycarbonylbenzoic acid was dissolved in 200 ml of THF under a flow of nitrogen, and 43.4 ml of borane dimethylsulfide complex was added with stirring under ice-cooling. After stirring for 18 hours, 200 ml of water was added, and then 96 g of potassium carbonate was added. It was extracted with ethyl acetate, and theorganic layer was washed with salt solution. After drying with magnesium sulfate, the resulting solid was dissolved in 800 ml of ethyl acetate, 750 mg of 10% Pd/C was added, and stirring was continued under the flow of hydrogen. After the reaction was completed, it was subjected to the filtration, and then the filtrate was concentrated to produce 64 g of the title compound. was added cooling After stirring for 18 hours It was extracted with ethyl acetate, and theorganic layer was washed with salt solution After drying with magnesium sulfate the resulting solid was dissolved in 800 ml of ethyl acetate 750 mg of 10% Pd/C was added stirring it was subjected to the filtration the filtrate was concentrated

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

Procedure: A mixture of the product from step (ii) (23.4 g), ammonium chloride (23 g) and iron powder (23 g) in methanol (200 ml) and water (200 ml) was heated at reflux for 1 hour. The mixture was filtered and concentrated under reduced pressure and the residue treated with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The extract was dried (MgSO4) and evaporated. Yield 19.38 g. was heated at reflux for 1 hour The mixture was filtered concentrated under reduced pressure the residue treated with saturated aqueous sodium bicarbonate extracted with ethyl acetate The extract was dried (MgSO4) evaporated

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

Procedure: Methyl 3-(hydroxymethyl)-5-nitrobenzoate (11.2 g, 53 mmol) in methanol (50 mL) was flushed with nitrogen, and treated with palladium (10% on charcoal, 1.1 g). The flask was flushed with hydrogen and allowed to stir under an atmosphere of hydrogen overnight. The reaction was flushed with nitrogen, filtered through celite, and concentrated. Column chromatography on silica gel (50% ethyl acetate/hexanes) afforded 2.8 g (29%). 1H-NMR (CD3OD, 300 MHz) δ 7.34 (s, 1H), 7.27 (s, 1H), 6.94 (s, 1H), 4.55 (s, 2H), 3.88 (s, 3H). Mass spec.: 182.09 (MH)+. The flask was flushed with hydrogen The reaction was flushed with nitrogen filtered through celite concentrated Column chromatography on silica gel (50% ethyl acetate/hexanes) afforded 2.8 g (29%)

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

Procedure: 85 g of 3-nitro-5-methoxycarbonylbenzoic acid was dissolved in 200 ml of THF under a flow of nitrogen, and 43.4 ml of borane dimethylsulfide complex was added with stirring under ice-cooling. After stirring for 18 hours, 200 ml of water was added, and then 96 g of potassium carbonate was added. It was extracted with ethyl acetate, and theorganic layer was washed with salt solution. After drying with magnesium sulfate, the resulting solid was dissolved in 800 ml of ethyl acetate, 750 mg of 10% Pd/C was added, and stirring was continued under the flow of hydrogen. After the reaction was completed, it was subjected to the filtration, and then the filtrate was concentrated to produce 64 g of the title compound. was added cooling After stirring for 18 hours It was extracted with ethyl acetate, and theorganic layer was washed with salt solution After drying with magnesium sulfate the resulting solid was dissolved in 800 ml of ethyl acetate 750 mg of 10% Pd/C was added stirring it was subjected to the filtration the filtrate was concentrated