2-AMINO-4-METHOXY-BENZOIC ACID METHYL ESTER

To a solution of 4-methoxyanthranilic acid (5.0 g, 30.0 mmol) in a mixtue of 10percent methanol in tetrahydrofuran (100 mL) was added dropwise (trimethylsilyl)diazomethane (2.0 M solution in diethyl ether, 18.0 mL, 36.0 mmol) at 0 °C. The reaction mixture was stirred for 16 hours at room temperature then quenched by the addition of glacial acetic acid (0.1 mL). The reaction mixture was concentrated and the residue was partitioned between saturated sodium bicarbonate (50 mL) and ethyl acetate (250 mL). The organic layer was separated and washed with water (50 mL), saturated sodium bicarbonate (50 mL) and brine (50 mL), dried over sodium sulfate, filtered and concentrated to give methyl 2-amino-4-methoxybenzoate as an oil (5.4 g, quantitative). MS (EI) for CTo a solution of 2-amino-4-(methyloxy) benzoic acid (5 g, 30 mmol) in MeOH (30 mL) and toluene (60 mL) wasadded trimethylsilyldiazomethane (30 mL, 60 mmol). The reaction mixture was stirred atooc for 1 h. The reaction mixture was allowed to warm to rt and solvent was removed in5 vacuo. The crude material was purified by column chromatography (0 to 15percentEtOAC/hexanes) to provide 4.2 g of the title compound (74percent). MS: m/z: 182 [M+HStep 1. Methyl 2-amino-4-methoxybenzoate: To a solution of 2-amino-4- (methyloxy) benzoic acid (5 g, 30 mmol) in MeOH (30 mL) and toluene (60 mL) was added trimethylsilyldiazomethane (30 mL, 60 mmol). The reaction mixture was stirred at 0°C for 1 h. The reaction mixture was allowed to warm to rt and solvent was removed in vacuo. The crude material was purified by column chromatography (0 to 15percent EtOAc/hexanes) to provide 4.2 g of the title compound (74percent). MS: m/z: 182 [M+H]To a solution of 2-amino-4-(methyloxy) benzoic acid (5 g, 30 mmol) in MeOH (30 mL) and toluene (60 mL) was added trimethylsilyldiazomethane (30 mL, 60 mmol). To a solution of 2-amino-4-methoxybenzoic acid 33 (5.0 g, 0.03 mol) in methanol (50 mL) was added strong sulphuricacid (9 mL). The solution was stirred at reflux for 24 h. Itwas cooled to room temperature and the pH of the mixturewas adjusted to 5~6 with saturated sodium carbonatesolution. The solution was extracted with EA (100 mL*2).The combined organic layers were washed with brine(50 mL), dried over Na2SO4, filtered and concentrated, affording white powder 34 (4.11 g, 75.92percent). 34: 1H NMR (400 MHz, CDCl3) 7.81 (d, J = 8.9 Hz, 1 H), 6.25 (dd, J =9.0, 2.5 Hz, 1H), 6.13 (d, J = 2.4 Hz, 1H), 5.80 (s, 2H), 3.86(s, 3H), 3.81 (s, 3H).Step a): Methyl 2-amino-4-methoxybenzoate

Molecular Weight:181.19
XLogP3:2.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:181.07389321
Monoisotopic Mass:181.07389321
Topological Polar Surface Area:61.6
Heavy Atom Count:13
Complexity:184
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes