5-BROMO-2-NAPHTHOICACID

To a boiling solution of 2-naphthoic acid (10.00 g, 58.14 mmol) in acetic acid (50 mL) is added dropwise bromine (3 mL) containing iodine (0.25 g). After the addition is complete, the solution is refluxed for 0.5 hr. A white precipitate forms during cooling and is isolated by filtration, washed with acetic acid and then water. The solid is triturated in methanol (100 mL) and 7.01 g (53.4percent yield) of the desired product is obtained as a white solid. m.p. 248-250° C. Preparation 3 [0106] Preparation of 6-Iodo-1-methoxy-naphthalene. [CHEMMOL-00022] [0107] Preparation of 5-Bromo-2-naphthalenecarboxylic acid. [0108] 2-Naphthoic acid (50;0 g, 0.290 mol), glacial acetic acid (250 mL), bromine (15 mL, 0.291 mol) and iodine (1.3 g, 0.005 mol) were combined in a flask under N2 atmosphere. The mixture was heated at reflux for 35 minutes then cooled to room temperature. The thick yellow mixture was stirred at room temperature for 1 hour. The mixture was filtered and the pale orange solid was rinsed with 100 mL of the filtrate. The solid was dried in vacuo at 55° C. overnight to yield 55.5 g of pale orange solid. The solid was slurried in 275 mL of 1 N NaOH for 30 minutes. The solid was filtered off and rinsed 3 times with 50 mL portions of the filtrate. The solid was air dried in the hood over the weekend to yield 46.7 g of solid. The solid was added to 220 mL of water. Concentrated HCl (15 mL) was added to obtain pH of 1.3 and the mixture was stirred for 4 hours. The solid was filtered off and washed with 200 mL of water. The solid was dried in vacuo at 50° C. to give 37.6 g of intermediate title compound as white crystals (HPLC: 90percent with 9percent 2-naphthoic acid, 46percent yield).To a boiling solution of 2-naphthoic acid (10.00 g, 58.14 mmol) in acetic acid (50 mL) is added dropwise bromine (3 mL) containing iodine (0.25 g). After the addition is complete, the solution is refluxed for 0.5 hr. A white precipitate forms during cooling and is isolated by filtration, washed with acetic acid and then water. The solid is triturated in methanol (100 mL) and 7.01 g (53.4percent yield) of the desired product is obtained as a white solid. m.p. 248-250° C. 1H NMR (300 MHz, CD3OD): delta 8.94 (d, J=1.8 Hz, 1H), 8.52-8.42 (m, 3H), 8.27 (dd, J=1.8, 7.5 Hz, 1H), 7.79 (t, J=8.4 Hz, 1H).Preparation 3 [0106] Preparation of 6-Iodo-1-methoxy-naphthalene. [CHEMMOL-00022] [0107] Preparation of 5-Bromo-2-naphthalenecarboxylic acid. [0108] 2-Naphthoic acid (50;0 g, 0.290 mol), glacial acetic acid (250 mL), bromine (15 mL, 0.291 mol) and iodine (1.3 g, 0.005 mol) were combined in a flask under N2 atmosphere. The mixture was heated at reflux for 35 minutes then cooled to room temperature. The thick yellow mixture was stirred at room temperature for 1 hour. The mixture was filtered and the pale orange solid was rinsed with 100 mL of the filtrate. The solid was dried in vacuo at 55° C. overnight to yield 55.5 g of pale orange solid. The solid was slurried in 275 mL of 1 N NaOH for 30 minutes. The solid was filtered off and rinsed 3 times with 50 mL portions of the filtrate. The solid was air dried in the hood over the weekend to yield 46.7 g of solid. The solid was added to 220 mL of water. Concentrated HCl (15 mL) was added to obtain pH of 1.3 and the mixture was stirred for 4 hours. The solid was filtered off and washed with 200 mL of water. The solid was dried in vacuo at 50° C. to give 37.6 g of intermediate title compound as white crystals (HPLC: 90percent with 9percent 2-naphthoic acid, 46percent yield).A. 5-Bromo-2-Naphthoic Acid A 75 g (0.44 mole) portion of 2-naphthoic acid, 375 ml of acetic acid, 22.5 ml of Br2 (70 g, 0.44 mole) and 1.9 g (0.015 mole) of I2 were placed in a 1 l. 3-necked flask and refluxed with stirring for 0.6 hours. The reaction mixture was cooled to 25° and filtered. The cream solid was washed with small portions of the filtrate, air dried and dried to a constant weight at 60° to give 76 g (75percent) of a light tan-cream solid, m.p. 224°-233° dec. The crude product was slurried with 375 ml of 1 N NaOH for 0.5 hours and filtered.2-Naphthoic acid (50.0 g, 0.290 mol), glacial acetic acid (250 mL), bromine (15 mL, 0.291 mol) and iodine (1.3 g, 0.005 mol) were combined in a flask under N2 atmosphere. The mixture was heated at reflux for 35 minutes then cooled to room temperature. The thick yellow mixture was stirred at room temperature for 1 hour. The mixture was filtered and the pale orange solid was rinsed with '100 mL of the filtrate. The solid was dried in vacuo at 55 C. overnight to yield 55.5 g of pale orange solid. The solid was slurried in 275 mL of 1 N NaOH for 30 minutes. The solid was filtered off and rinsed 3 times with 50 mL portions of the filtrate. The solid was air dried in the hood over the weekend to yield 46.7 g of solid. The solid was added to 220 mL of water. Concentrated HCl (15 mL) was added to obtain pH of 1.3 and the mixture was stirred for 4 hours. The solid was filtered off and washed with 200 mL of water. The solid was dried in vacuo at 50 C. to give 37.6 g of intermediate title compound as white crystals (HPLC: 90percent with 9percent 2-naphthoic acid, 46percent yield).

Molecular Weight:251.08
XLogP3:3.4
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