6-Bromo-2-naphthalenecarboxylic acid

Pale brown solid

General procedure: Compound 14 (4.58 g, 20 mmol) in 1:1 THF/HA suspension of methyl 6-bromo-2-naphthoate (3b) (2.7 g, 10.0 mmol) and potassium hydroxide (1.1 g, 20.0 mmol) in methanol (50 mL) was vigorously stirred at 50 °C. The reaction mixture becomes homogeneous after the consumption of the initial compound 3b. After 8 h, the solvent was evaporated under reduced pressure (ca 2/3 vol.), water (1500 mL) was added and the unreacted ester extracted with ethyl acetate. The aqueous solution was acidified with 10percent HExample 176-BROMONAPHTHALENE-2-CARBOXYLIC ACID [(R)-1-(4-METHANESULFONYLAMINO-3-METHYLPHENYL)ETHYL]AMIDE 17A) 6-BROMONAPHTHALENE-2-CARBOXYLIC ACID To a stirred solution of 6-bromonaphthalene-2-carboxylic acid methyl ester (2 g, 8 mmol) in tetrahydrofuran (66 mL) and ethanol (22 mL) was added a solution of lithium hydroxide (542 mg, 22 mmol) in water (22 mL). The reaction was stirred at 50° C. for 16 hours. After cooling, the organic solvents were removed by evaporation, and the aqueous residue was diluted with water (100 mL) then washed with EtOAc (2.x.50 mL). The aqueous layer was acidified using 1N HCl and the products were extracted with EtOAc (3.x.50 mL). The combined organics were washed with brine (100 mL), dried (MgSOPart A. Preparation of 6-bromo-2 -naphthoic acid.; [00746] A solution of methyl 6-bromo-2-naphthoate (7.7Og, 29.0mmol) in 2:1 THF:water (15OmL) was treated with lithium hydroxide hydrate (2.44g, 58.1mmol) followed by stirring at room temperature for 48h. Concentrated under vacuum, diluted with water and cooled to O[00487] Example 1. Preparation ofN-(6-(3-tert-butyl-5-(2, 4-dioxotetrahydropyrimidin-l(2H)-yl)-2- methoxyphenyl)naphthalen-2-yl)methanesulfonamide (compound IA-LO-2.9).; [00488] Part A. Preparation of 6-bromo-2 -naphthoic acid.; [00489] A solution of methyl 6-bromo-2-naphthoate (7.7Og, 29.0mmol) in 2:1 THF:water (15OmL) was treated with lithium hydroxide hydrate (2.44g, 58.1mmol) followed by stirring at room temperature for 48h. Concentrated under vacuum, diluted with water and cooled to OPart H. Preparation of 6-bromo-2 -naphthoic acid.[00326] A solution of methyl 6-bromo-2-naphthoate (7.7Og, 29.0mmol) in 2: 1 tetrahydrofuran: water(150 mL) was treated with lithium hydroxide hydrate (2.44 g, 58.1 mmol) followed by stirring at room temperature for 48 hours. The mixture was concentrated under vacuum, diluted with water and cooled to 0 Potassium hydroxide (127 mg, 2.26 mmol) was added to a suspension of methyl 6-bromo-2-naphthoate (200 mg, 0.75 mmol) in methanol (50 mL) and the mixture heated at 50 °C for 48 h. The solvent was evaporated and the residue diluted with water (30 mL), acidified with HCl (1 M) and the extracted with ethyl acetate (30 mL * 2). The combined organic layers were dried with anhydrous magnesium sulfate and the solvent evaporated under reduced pressure. The crude product was purified via recrystallization using ethyl acetate to give the product as white crystals (105 mg, yield 56percent). 1-(6-bromo-naphthalen-2-yl)ethaneone (0.22 g, 0.88 mmol) obtained in Preparation Example 100 was dissolvedin 3 mL of 1, 4-dioxane. NaOH (0.353 g, 8.8 mmol) dissolved in 3 mL of water and 9-11percent NaOCl solution (1.67mL, 2.64 mmol) were added thereto, and the mixture was heated to 70°C and stirred for 4 hours. After addition of NaHSO3aqueous solution and water, the reaction solution was extracted with ether. 1N HCl was added thereto, and the organiclayer was separated, dried with MgSO4 and purified by column chromatography to obtain the title compound (0.156 g, 70percent).1H-NMR (CDCl3) δ 8.56 (1H, s), 8.05 (2H, m), 7.79 (2H, m), 7.58 (1H, m).6-bromo-2-naphthalenecarboxylic acid (Compound M) 6-bromo-2-naphthalenecarboxylic acid (Compound M) A glass container of 500 ml, provided with a reflux condenser, a gas injecting tube, an exhaust tube, a temperature measurement tube, and an electromagnetic stirrer, was set up with 210 g (3.5 mol) of acetic acid, 1.66 g (6.66 mmol) of cobalt acetate tetrahydrate, 1.65 g (6.73 mmol) of manganese acetate tetrahydrate, 1.06 g (8.91 mmol) of potassium bromide, 10.0 g (45 2 mmol) of 6-bromo-2-methylnaphthalene, and 5.2 g (51.0 mmol) of acetic acid anhydride. An oxidation reaction for producing BNA was performed by stirring the mixture in the glass container during 4.5 hours under ordinary pressure while keeping the inner temperature of the glass container at 110 degrees C. and injecting pure oxygen with a flow rate of 0.2 litters/minute into the glass container. [0043] After completing the reaction and cooling the reaction liquid to 30 degrees C., the cooled liquid was filtrated to obtain a precipitate as a residue. The obtained residue was dried under reduced pressure of 5 mmHg and 40 degrees C. until being of constant mass. A crude BNA product was thus obtained with a purity of 99.2percent and a weight of 8.29 g.6-bromo-2-naphthol crystals. Finally, the crude crystals were reintroduced to a mass fraction of 66.7percent with a mass of 2160 Kg Of the acetic acid solution in the re-dissolved, dissolved and then static 1. 5h, filtration, washing, After drying, a recrystallization of 6-bromo-2-naphthoic acid was obtained in a yield of 95. 3percent pure Degrees 99. 55percent, single miscellaneous 0. 45percent

Molecular Weight:251.08
XLogP3:4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:249.96294
Monoisotopic Mass:249.96294
Topological Polar Surface Area:37.3
Heavy Atom Count:14
Complexity:229
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes