5-AMINO-2-BROMO-BENZOIC ACID METHYL ESTER

To a mixture of methyl 2-bromo-5-nitro-benzoate (1.5 g, 5.8 mmol) and NHTo a clean, dry round bottom flask was added methyl 2-bromo-5-iodobenzoate (2.10 g, 6.16 mmol), dimethylformamide (60 mL), and Zn(CN)Reference 7-Bromo-8-methoxycarbonyl-3, 3-dimethyl-3, 4-dihydro-1H-quinoxalin-2-one (Reference Compound No.1) Methyl 5-amino-2-bromobenzoate (Reference Compound No.1-(1)) Methyl 2-bromo-5-nitrobenzoate (25.3 g, 97.3 mmol) was dissolved in anhydrous methanol (500 mL), Tin (II) chloride (93.3 g, 487 mmol) was added thereto, and then the reaction mixture was refluxed for 2 hours. The reaction mixture was cooled down, ethyl acetate (500 mL) and water (100 mL) were added thereto, the mixture was neutralized with 4N aqueous sodium hydroxide solution, and then filtered on celite. The filtrate was concentrated under reduced pressure, ethyl acetate (200 mL) was added thereto, and then the mixture was washed with saturated aqueous sodium hydrogen carbonate solution (200 mL, 2 times), water (200 mL), and saturated brine (200 mL) successively. The organic layer was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure to give the titled reference compound (21.0 g) as a pale yellow oil. (Yield 94percent) [Show Image] Methyl 2-bromo-5-nitrobenzoate (25.3 g, 97.3 mmol) was dissolved in anhydrous methanol (500 mL), tin (II) chloride (93.3 g, 487 mmol) was added thereto, and then the reaction mixture was refluxed for 2 hours. The reaction mixture was cooled down, ethyl acetate (500 mL) and water (100 mL) were added thereto, the mixture was neutralized with 4N aqueous sodium hydroxide solution, and then filtered on celite. The filtrate was concentrated under reduced pressure, ethyl acetate (200 mL) was added thereto, and then the mixture was washed with saturated aqueous sodium hydrogen carbonate solution (200 mL, twice), water (200 mL), and saturated brine (200 mL) successively. The organic layer was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure to give the titled reference compound (21.0 g) as a pale yellow oil. (Yield 94percent) Methyl 5-amino-2-bromobenzoate (Reference Compound No.1-(1))EXAMPLE 55-58Preparation of Methyl 5-(dimethylamino)-2-(7-hydroxy-4, 5Preparation 20 (A) At room temperature, To a solution of methyl 2-bromo-5-nitrobenzoate (5.0 g)And acetic acid (100 mL)The mixture was added with zinc powder (12.57 g)The resulting mixture was stirred at the same temperature for 10 minutes.After filtering the reaction mixture, the solvent was removed by distillation under reduced pressure.Saturated aqueous sodium bicarbonate was added to the residue, and the aqueous layer was extracted with ethyl acetate.The extract was washed with water and brine, Dried over anhydrous magnesium sulfate, And the solvent was removed by distillation under reduced pressure to obtain the title compound (4.92 g).To a solution of 5-amino-2-bromobenzoic acid (4-1)(2.00 g, 9.26 mmol, commercially available compound) and anhydrous methanol (40 mL)Of concentrated solution was added concentrated sulfuric acid (4 mL)And the mixture was stirred at an external temperature of 70 ° C for 18 hours.The solvent was distilled off under reduced pressure, After adding 4M aqueous sodium hydroxide solution (12 mL)Ethyl acetate (30 mL) was added, Water (30 mL) and extracted.Water (30 mL), Saturated brine (30 mL) The organic layer was further washed and dried over anhydrous magnesium sulfate, The solvent was distilled off under reduced pressure to give the title compound (4-2) (0.941 g, yield: 44percent).Production of Methyl 5-Amino-2-bromobenzoate (4-2)

Molecular Weight:230.06
XLogP3:2.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:228.97384
Monoisotopic Mass:228.97384
Topological Polar Surface Area:52.3
Heavy Atom Count:12
Complexity:174
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes