methyl 3-amino-4-hydroxybenzoate

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

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

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

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: A stirred mixture of methyl 4-hydroxy-3-nitrobenzoate (3.22 g, 0.0163 mol) and 5% Pd-C (12.9 g) in MeOH (30 mL) was hydrogenated under an atmospheric pressure for 70 hr at room temp. Insoluble catalyst was removed, and the filtrate was evaporated in vacuo. The residue was chromatographed on silica-gel with EtOH—CHCl3 (1:20, v/v) as eluent to afford 1.89 g (69%) methyl 3-amino-4-hydroxybenzoate as a pale brown syrup. Insoluble catalyst was removed the filtrate was evaporated in vacuo The residue was chromatographed on silica-gel with EtOH—CHCl3 (1:20, v/v) as eluent

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

Procedure: A stirred mixture of methyl 4-hydroxy-3-nitrobenzoate (3.22 g, 0.0163 mol) and 5% Pd—C (12.9 g) in MeOH (30mL) was hydrogenated under an atmospheric pressure for 70 hr at room temp. Insoluble catalyst was removed, and the filtrate was evaporated in vacuo. The residue was chromatographed on silica-gel with EtOH—CHCl3 (1:20, v/v) as eluent to afford 1.89 g (69%) methyl 3-amino-4-hydroxybenzoate as a pale brown syrup. Insoluble catalyst was removed the filtrate was evaporated in vacuo The residue was chromatographed on silica-gel with EtOH—CHCl3 (1:20, v/v) as eluent

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

Procedure: To an ice-cold, stirred solution of methyl 3-amino-4-hydroxybenzoate (3.0 g) and sodium bicarbonate (3.3 g) in 1:1 isobutyl methyl ketone/water (40 mL) was added chloroacetyl chloride (1.7 mL), and the mixture was stirred for 1 h. The mixture was warmed to room temperature and refluxed for 14 h, cooled to room temperature, diluted with chloroform, and separated. The organic layer was washed with water, and brine, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:9 methanol/chloroform) afforded a phenoxazine 3.2 g as a white solid, which was used without further purification or characterization. To a solution of phenoxazine from step 1 (700 mg) and potassium carbonate (934 mg) in methanol (8 mL) was added bromobutane (1.8 mL), and the mixture was refluxed for 6 d. The mixture was cooled to room temperature, concentrated under reduced pressure, and the residue was partitioned between ethyl acetate and water. The organic layer washed with brine, dried (magnesium sulfate), filtered, and concentrated under reduced pressure to afforded 800 mg of the title compound: 1H NMR (300 MHz, CDCl3) δ 7.72–7.68, 7.02–6.99, 4.66, 4.00–3.92, 1.69–1.64, 1.46–1.38, 1.01–0.95. refluxed for 14 h cooled to room temperature separated The organic layer was washed with water, and brine dried (magnesium sulfate) filtered concentrated under reduced pressure Purification by flash column chromatography (silica, 1:9 methanol/chloroform)

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

Procedure: A mixture of methyl 3-amino-4-hydroxybenzoate (2.5 g, 15 mmol) and methyl 4-formylbenzoate (2.46 g, 15 mmol) in methanol (75 mL) was stirred at rt overnight. The solvent was evaporated under reduced pressure and the remaining residue was dissolved in dichloromethane (150 mL). DDQ (3.5 g, 15.4 mmol) was added and the reaction mixture was stirred at rt for 1 h. Saturated NaHCO3 (200 mL) was added. The suspension was filtered off, the resulting solid was washed with saturated NaHCO3 (50 mL), water (50 mL), and ethyl acetate (100 mL) and dried in vacuo to give compound 1 (4 g, 86% yield) as yellow solid. The solvent was evaporated under reduced pressure the remaining residue was dissolved in dichloromethane (150 mL) the reaction mixture was stirred at rt for 1 h The suspension was filtered off the resulting solid was washed with saturated NaHCO3 (50 mL), water (50 mL), and ethyl acetate (100 mL) dried in vacuo

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-amino-4-methoxycarbonylphenol [Acta Chimica Academiae Scientiarum Hungaricae, 99(1), 49-50 (1979)] (5.0 g) in dimethylformamide (30 ml) were added potassium carbonate (8.3 g) and 2-chloropropionyl chloride (4.0 g) and the mixture was stirred at 50° C. for 2 hours. Water was added to the reaction solution and extraction with ethyl acetate was conducted. The extraction was concentrated and hexane was added thereto to give precipitates, which were taken by filtration and dried to give 6-methoxycarbonyl-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine (4.7 g). The extraction was concentrated hexane was added to give precipitates which were taken by filtration dried

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

Procedure: To solution of 2-amino-4-methoxycarbonylphenol [Acta Chimica Academiae Scientiarum Hungaricae, 99 (1), 49-50 (1979)] (4.78 g) in a mixed solvent of ethyl acetate (50 ml) and water (50 ml) were added sodium hydrogen carbonate (3.6 g) and 2-bromoisobutyryl bromide (6.90 g) and the mixture was stirred at room temperature for 10 minutes. The organic layer was separated and the solvent was distilled off under reduced pressure. The resulting residue was dissolved in dimethylformamide (70 ml), to the solution was added potassium carbonate (4.35 g) and the mixture was stirred at room temperature for a day. The reaction solution was poured into water to give precipitates, which were taken by filtration and dried to give 2,2-dimethyl-6-methoxycarbonyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine (5.4 g). The organic layer was separated the solvent was distilled off under reduced pressure The resulting residue was dissolved in dimethylformamide (70 ml), to the solution was added potassium carbonate (4.35 g) the mixture was stirred at room temperature for a day The reaction solution was poured into water to give precipitates which were taken by filtration dried

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 21.3 g of methyl 3-amino-4-hydroxybenzoate and 23 g of 2,3-dichloropyrazine were added to 40 ml of dry N,N-dimethylformamide and the resulting mixture was stirred under heating to 160° C. for 6 hours. Then the reaction mixture was brought back to room temperature and the crystals thus precipitated were taken up by filtration and washed with ethyl acetate. Thus 23 g of the title compound was obtained as brown crystals. was brought back to room temperature the crystals thus precipitated were taken up by filtration washed with ethyl acetate