Methyl 2,3-diaminobenzoate

Yellow Solid

To a nitrogen-saturated solution of 2-amino-3-nitrobenzoic acid methyl ester (Chess GmbH, 50 g, 0.26 mol) in absolute ethanol (800 mL) was added palladium hydroxide (Degussa, 20percent w/w on carbon, 58.75percent w/w water, 10 g). Methyl 2-amino-3-nitrobenzoate (117; 3.2 g) was dissolved in EtOAc (100 mL) and10percent Pd on C (200 mg) was added. The resulting reaction mixture was hydrogenated under 1 atm of hydrogen at room temperature for 2 days and filtered through a pad of Celite. The filtrate was concentrated under reduced pressure to afford essentially quantitative yield of methyl 2, 3-diaminobenzoate 118.21a) Methyl 2, 3-diaminobenzoate10percent Palladium on carbon (0.25 g) was placed in a 3-neck round bottom flask then flushed with nitrogen and evacuated. This was repeated several times, then ethanol (100 mL) was added to the flask. Partially dissolved methyl 2-amino-3- nitrobenzoate (3.5 g, 17.8 mmol) in ethanol (60 mL) was added, and the reaction mixture purged with nitrogen and evacuated. The reaction mixture was left to stir under hydrogen (1.6 L). After stirring for 24 h, the reaction mixture was filtered over a pad of Celite(4) Reference Example 3 Methyl 2-amino-3-nitrobenzoate (10 g, 51 mmol) was dissolved in ethanol (500 mL)under nitrogen. Palladium on carbon (10percent w/w, 2.7 g, 2.6 mmol) was added undernitrogen. The reaction was placed under a hydrogen atmosphere (1 atm) and stirredfor 16 h at room temperature. The reaction was flushed with nitrogen, filtered throughdiatomaceous earth and concentrated to provide the product (8.39 g, 99percent) as awhite solid. 2) 10percent Palladium carbon (water content 51.7percent, 250 mg) was added to a solution of methyl ester of 2-amino-3-nitrobenzoic acid (980 mg, 5.00 mmol) in methanol (20 ml)-tetrahydrofuran (10 ml) and the mixture was stirred under hydrogen atmosphere at room temperature for 3 hrs. The catalyst was removed by filtration and washed with tetrahydrofuran. The filtrate and washings were combined and the solvent was distilled off under reduced pressure to give methyl ester of 2, 3-diaminobenzoic acid (814 mg, 98percent) as a yellowish green solid. m.p.: 65-67° C.; IR (Nujol) : 3451, 3314, 1701, 1619 cmTin(II)chloride dihydrate (17.25 g, 76.5 mmol) was added in one portion to methyl 2-amino-3-nitrobenzoate (5.0 g, 25.5 mmol) in methanol (100 mL) under nitrogen. The yellow mixture was vigorously stirred at 65 Methyl 2-amino-3-nitrobenzoate (2.5g, 12.75mmol) dissolved in 20mL methanol, Palladium-carbon (500 mg) was added. The mixture was stirred at room temperature under a hydrogen atmosphere for 24 h, palladium on carbon was removed by filtration, the filtrate was concentrated, and the residue was subjected to column chromatography to give the titled compound (2 g, yield 95percent) as a brown solid2-amino-3-nitrobenzoic acidMethyl ester (Z-1)(500 mg, 2.78 mmol, commercially available compound) was added acetic acid (10 mL)After heating to 50 ° C, zinc powder (1.67 g, 25.5 mmol) was added, Stir for 30 minutes.The reaction solution was allowed to cool, After filtering the zinc powder, The solvent was distilled off under reduced pressure, To the resulting residue was added ethyl acetate (15 mL) and saturated aqueous sodium bicarbonate (15 mL) and extracted.The organic layer was washed successively with water (15 mL) and saturated brine (15 mL)After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, To give the title compound (9-1) (391 mg, yield 94percent).Production of Methyl 2, 3-Diaminobenzoate (9-1) After dissolving 2-amino-3-nitrobenzoic acid methyl ester (661 mg, 3.37 mmol) in methanol (30 ml), 10percent palladium-carbon powder (5 molpercent) was added under a nitrogen stream, and the mixture was stirred for 1 hour under a hydrogen atmosphere. The reaction mixture was filtered through celite, and the obtained filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate = 2/1) to obtain 2, 3-diaminobenzoic acid methyl ester. The compound was identified by NMR. Yield: 517.2 mg (92percent).1H-NMR (270 MHz, CDCl3): δ7.46(1H, dd, J=8.2Hz, 1.5Hz), 6.85(1H, dd, J=8.2Hz, 1.5Hz), 6.60(1H, t, J=8.2Hz), 5.53(br), 3.87(3H, s), 3.35(br) ppm.To a suspension of methyl 2-amino-3-nitrobenzoate (15 g, 76.5 mmol) in methanol (800 mL) was added 10percent palladium on carbon (50percent wet; 6.5 g) , and the mixture was stirred at room temperature for 20 hours under hydrogen atmosphere. The catalyst was removed by filtration, and the filtrate was concentrated in vacuo. The residual solid was crystallized from diisopropyl ether-hexane to give 11.57 g (69.6 mmol, 91.0percent) of the title compound as a dark yellow needle .(IV) The product just obtained in stage (III) (30 g), in methanol (1.5 I), was hydrogenated for 3 h using 10 percent Pd/C (3 g). The reaction mixture was filtered and concentrated to obtain the desired product. Yield: 90 percentStep 5: 2, 3-Diamino-benzoic acid methyl ester ; To a solution of 2-amino-3-nitro-benzoic acid methyl ester (2 g, 10 mmol) in methanol, a suspension of 10percent Pd/C (300 mg) in methanol 5 ml. was added and hydrogenated with a hydrogen balloon over a period of 8 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to obtain 1.5 g of the required compound as a brown coloured solid (88percent).1H NMR (300 MHz, DMSOd6): δ (ppm) = 7.09(dd, 1 H, J=8.1 ; 1.2 Hz), 6.70(dd, 1 H, J=8.1 ; 1.2 Hz), 6.3.8(m, 1 H), 6.199(s, 2H), 4.77(s, 2H), 3.76(s, 3H).10 percent Palladium carbon (water content 51.7 percent, 250 mg) was added to a solution of methyl ester of 2-amino-3-nitrobenzoic acid (980 mg, 5.00 mmol) in methanol (20 ml)-tetrahydrofuran (10 ml) and the mixture was stirred under hydrogen atmosphere at room temperature for 3 hrs. The catalyst was removed by filtration and washed with tetrahydrofuran. The filtrate and washings were combined and the solvent was distilled off under reduced pressure to give methyl ester of 2, 3-diaminobenzoic acid (814 mg, 98percent) as a yellowish green solid. m.p.: 65 - 67°C; IR (Nujol): 3451, 3314, 1701, 1619 cm-1; APCI-MS m/z: 167 [M+H]+Reference

Molecular Weight:166.18
XLogP3:1.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:166.074227566
Monoisotopic Mass:166.074227566
Topological Polar Surface Area:78.3
Heavy Atom Count:12
Complexity:172
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes