methyl 2-amino-3-hydroxybenzoate

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

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

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of methyl 3-hydroxy-2-nitrobenzoate (14 g, 71 mmol) and 10% Pd/C (1.4 g) in ethyl acetate (300 mL) was purged in 1 atm hydrogen and stirred at 25° C. for 4 hr. The mixture was filtered, and the filtrate was concentrated to give methyl 2-amino-3-hydroxybenzoate (11.5 g, yield 97%) as a light yellow solid. 1H-NMR (400 MHz, CDCl3-d) δ 3.88 (s, 1H), 5.84 (s, br 3H), 6.50-6.54 (t, J=8.0 Hz, 1H), 6.84-6.86 (d, J=7.2 Hz, 1H), 7.47-7.49 (d, J=7.6 Hz, 1H); LC-MS (ESI) m/z 168 [M+1]+. was purged in 1 atm hydrogen The mixture was filtered the filtrate was concentrated

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

Procedure: A solution of 1.0 g (4.9 mmol) of methyl 2-amino-3-hydroxybenzoate 9a, 1.03 g (7.4 mmol) of 4-fluorobenzoic acid 9b, 10 mL DMF and 2.9 mL (20.6 mmol) of TEA were placed into a flask and stirred for 10 min. HATU (7.4 mmol, 2.8 g) was added and the reaction was stirred overnight. The reaction mixture was poured into water and extracted with EtOAc. The organics were washed with water and brine and the solvent was evaporated to give 1.2 g of crude product, methyl 2-(4-fluoro-benzoylamino)-3-hydroxy-benzoate, 9c, which was used without purification. MS m/z (M+H+) 290.1. the reaction was stirred overnight extracted with EtOAc The organics were washed with water and brine the solvent was evaporated

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

Procedure: A solution of 1.0 g (4.9 mmol) of methyl 2-amino-3-hydroxybenzoate 9bb, 1.03 g (7.4 mmol) of 4-fluorobenzoic acid 9 cc, 10 mL DMF and 2.9 mL (20.6 mmol) of TEA were placed into a flask and stirred for 10 min. HATU (7.4 mmol, 2.8 g) was added and the reaction was stirred overnight. The reaction mixture was poured into water and extracted with EtOAc. The organics were washed with water and brine and the solvent was evaporated to give 1.2 g of crude product, methyl 2-(4-fluoro-benzoylamino)-3-hydroxy-benzoate, 9dd, which was used without purification. MS m/z (M+H+) 290.1. the reaction was stirred overnight extracted with EtOAc The organics were washed with water and brine the solvent was evaporated

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

Procedure: A solution of 0.22 g (1.32 mmol) of methyl-2-amino-3-hydroxybenzoate, 0.77 mL (4.6 mmol) of triethylorthoformate and 0.066 g (0.26 mmol) of pyridinium p-toluene sulfonate in 15 mL of xylene was heated at reflux for 18 h. The reaction mixture was concentrated and purified by chromatograph (silica, hexanes:EtOAc, 6:1) to give 0.22 g of the title compound. at reflux for 18 h The reaction mixture was concentrated purified by chromatograph (silica, hexanes:EtOAc, 6:1)

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

Procedure: To a solution of 2 g (13.1 mmol) of 2-amino-3-hydroxybenzoic acid in 60 mL of CH3OH at 0° C. was bubbled HCl gas until the solution was saturated. The reaction was heated at reflux for 12 h. The reaction mixture was concentrated and dissolved in 30 mL of water. The solution was neutralized with sat'd NaHCO3 solution and extracted with EtOAc. The organic fractions were dried over MgSO4, filtered and the filtrate was concentrated to give 1.8 g of the title compound as a brown solid. The reaction was heated at reflux for 12 h The reaction mixture was concentrated dissolved in 30 mL of water extracted with EtOAc The organic fractions were dried over MgSO4 filtered the filtrate was concentrated

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 2-amino-3-hydroxybenzoate (882 mg) in pyridine (2 ml) was added acetic anhydride (1.2 ml) and the mixture was stirred at 20° C. for 8 hours. The reaction mixture was diluted with diisopropyl ether, and the resulting solid was collected and washed with diisopropyl ether. The solid was triturated with diisopropyl ether to give methyl 2-acetamido-3-acetoxybenzoate (1.25 g) as solid. the resulting solid was collected washed with diisopropyl ether The solid was triturated with diisopropyl ether

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 2-amino-3-hydroxybenzoate (882 mg) in pyridine (2 ml) was added acetic anhydride (1.2 ml) and the mixture was stirred at 20° C. for 8 hours. The reaction mixture was diluted with diisopropyl ether, and the resulting solid was collected and washed with diisopropyl ether. The solid was triturated with diisopropyl ether to give methyl 2-acetamido-3-acetoxybenzoate (1.25 g) as solid. the resulting solid was collected washed with diisopropyl ether The solid was triturated with diisopropyl ether

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

Procedure: To a solution of di (1H-imidazole-1-yl)methanamine (2.05 g, 12.26 mmol) in THF (60 mL) was added methyl-2-amino-3-hydroxybenzoate (1.98 g, 12.26 mmol) at room temperature and the resulting reaction mixture was heated to reflux for 17 h. The reaction mixture was cool to room temperature, diluted with EtOAc (100 mL) and washed with H2O (3×100 mL), saturated ammonium chloride (2×100 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was purified by recrystallization from diethyl ether to afford methyl 2-aminobenzoxazole-4-carboxylate (1.10 g, 50%) as a brown solid. 1H NMR and MS consistent. the resulting reaction mixture was heated to reflux for 17 h washed with H2O (3×100 mL), saturated ammonium chloride (2×100 mL) dried (Na2SO4) filtered concentrated under reduced pressure The crude material was purified by recrystallization from diethyl ether

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

Procedure: To a solution of di (1H-imidazole-1-yl)methanamine (2.05 g, 12.26 mmol) in THF (60 mL) was added methyl-2-amino-3-hydroxybenzoate (1.98 g, 12.26 mmol) at room temperature and the resulting reaction mixture was heated to reflux for 17 h. The reaction mixture was cool to room temperature, diluted with EtOAc (100 mL) and washed with H2O (3×100 mL), saturated ammonium chloride (2×100 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was purified by recrystallization from diethyl ether to afford methyl 2-aminobenzoxazole-4-carboxylate (1.10 g, 50%) as a brown solid. 1H NMR and MS consistent. the resulting reaction mixture was heated to reflux for 17 h washed with H2O (3×100 mL), saturated ammonium chloride (2×100 mL) dried (Na2SO4) filtered concentrated under reduced pressure The crude material was purified by recrystallization from diethyl ether

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

Procedure: To a solution of di(1H-imidazole-1-yl)methanamine (2.05 g, 12.26 mmol) in THF (60 mL) was added methyl-2-amino-3-hydroxybenzoate (1.98 g, 12.26 mmol) at room temperature and the resulting reaction mixture was heated to reflux for 17 h. The reaction mixture was cooled to room temperature, diluted with EtOAc (100 mL) and washed with H2O (3×100 mL), saturated ammonium chloride (2×100 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was purified by recrystallization from diethyl ether to afford methyl 2-aminobenzoxazole-4-carboxylate (1.10 g, 50%) as a brown solid. 1H NMR and MS consistent. the resulting reaction mixture was heated to reflux for 17 h washed with H2O (3×100 mL), saturated ammonium chloride (2×100 mL) dried (Na2SO4) filtered concentrated under reduced pressure The crude material was purified by recrystallization from diethyl ether