* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Preparation of 5-Bromo-2-naphthalenecarboxylic acid, Methyl Ester. [0110] 5-Bromo-2-naphthoic acid (17.33 g, 69 mmol) and 250 mL of MeOH were combined in a flask under N2 atmosphere. Thionyl chloride (5.84 mL, 80 mmol) was added dropwise over 15 minutes at a temperature of 25-30° C., resulting in a pale yellow mixture. The mixture was heated at reflux for 3 1/4 hours. The resulting yellow solution was concentrated in vacuo to 137.4 g of solution then placed in a freezer overnight. The resulting thick mixture was filtered and the solid was washed with 100 mL of cold MeOH. The solid was dried in vacuo at 50° C. to give 11.39 g of the intermediate title compound as white crystals. A second crop was filtered and washed with 100 mL of cold MeOH. The solid was dried to 1.31 g of white crystals. Yield: 69percent, 2 crops.
Reference：
[1] Synthetic Communications, 2011, vol. 41, # 13, p. 2017 - 2024
[2] Patent: US2004/6229, 2004, A1, . Location in patent: Page/Page column 15
[3] Helvetica Chimica Acta, 1938, vol. 21, p. 62,65
[4] Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 1893 - 1899
[5] Patent: WO2017/147328, 2017, A1, . Location in patent: Paragraph 0328
2
[ 1013-83-8 ]
[ 67878-76-6 ]
Yield
Reaction Conditions
Operation in experiment
69%
at 25℃; for 4 h; Heating / reflux
5-Bromo-2-naphthoic acid (17.33 g, 69 mmol) and 250 mL of MeOH were combined in a flask under N2 atmosphere. Thionyl chloride (5.84 mL, 80 mmol) was added dropwise over 15 minutes at a temperature of 25-30 C. resulting in a pale yellow mixture. The mixture was heated at reflux for 3? hours. The resulting yellow solution was concentrated in vacuo to 137.4 g of solution then placed in the freezer overnight. The resulting thick mixture was filtered and the solid was washed with 100 mL of cold MeOH. The solid was dried in vacuo at 50 C. to give 11.39 g of intermediate title compound as white crystals. A second crop was filtered and washed with 100 mL of cold MeOH. The solid was dried to 1.31 g of white crystals. Yield: 69percent, 2 crops.
With bromine; iodine In acetic acid for 0.5 h; Heating / reflux
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): δ 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).
46%
With bromine In acetic acid for 0.583333 h; Heating / reflux
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).
Reference：
[1] Patent: US2008/58423, 2008, A1, . Location in patent: Page/Page column 9
[2] Patent: US2004/6229, 2004, A1, . Location in patent: Page/Page column 15
[3] Synthetic Communications, 2011, vol. 41, # 13, p. 2017 - 2024
[4] Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 1893 - 1899
[5] Helvetica Chimica Acta, 1938, vol. 21, p. 62,65
[6] Chemische Berichte, 1876, vol. 9, p. 1519
[7] Journal fuer Praktische Chemie (Leipzig), 1891, vol. <2> 43, p. 427
[8] Chemische Berichte, 1876, vol. 9, p. 1519
[9] Australian Journal of Chemistry, 1965, vol. 18, p. 1351 - 1364
[10] ChemMedChem, 2010, vol. 5, # 1, p. 65 - 78
[11] Patent: US3932452, 1976, A,
[12] Patent: US2003/225281, 2003, A1, . Location in patent: Page 13
4
[ 19125-84-9 ]
[ 1013-83-8 ]
Reference：
[1] Journal of the American Chemical Society, 1937, vol. 59, p. 2561,2564
5
[ 13720-04-2 ]
[ 1013-83-8 ]
Reference：
[1] Journal of the American Chemical Society, 1937, vol. 59, p. 2561,2564
6
[ 556107-64-3 ]
[ 1013-83-8 ]
Reference：
[1] Chemische Berichte, 1876, vol. 9, p. 1519
7
[ 67878-76-6 ]
[ 1013-83-8 ]
Reference：
[1] Journal of Fluorine Chemistry, 1988, vol. 38, p. 139 - 152
8
[ 613-46-7 ]
[ 1013-83-8 ]
Reference：
[1] Chemische Berichte, 1876, vol. 9, p. 1519
9
[ 10035-10-6 ]
[ 64-19-7 ]
[ 1013-83-8 ]
Reference：
[1] Journal of the University of Bombay, Science: Physical Sciences, Mathematics, Biological Sciences and Medicine, 1946, vol. 15/3 A, p. 21
10
[ 10035-10-6 ]
[ 64-19-7 ]
[ 1013-83-8 ]
Reference：
[1] Journal of the University of Bombay, Science: Physical Sciences, Mathematics, Biological Sciences and Medicine, 1946, vol. 15/3 A, p. 21
11
[ 10035-10-6 ]
[ 64-19-7 ]
[ 1013-83-8 ]
Reference：
[1] Journal of the University of Bombay, Science: Physical Sciences, Mathematics, Biological Sciences and Medicine, 1946, vol. 15/3 A, p. 21
12
[ 82408-29-5 ]
[ 7726-95-6 ]
[ 64-19-7 ]
[ 1013-83-8 ]
Reference：
[1] Journal of the Indian Chemical Society, 1946, vol. 23, p. 427,428[2] Journal of the University of Bombay, Science: Physical Sciences, Mathematics, Biological Sciences and Medicine, 1946, vol. 15/3 A, p. 21,22
13
[ 88639-90-1 ]
[ 7726-95-6 ]
[ 64-19-7 ]
[ 1013-83-8 ]
Reference：
[1] Journal of the Indian Chemical Society, 1946, vol. 23, p. 427,428[2] Journal of the University of Bombay, Science: Physical Sciences, Mathematics, Biological Sciences and Medicine, 1946, vol. 15/3 A, p. 21,22
14
[ 88639-91-2 ]
[ 7726-95-6 ]
[ 64-19-7 ]
[ 1013-83-8 ]
Reference：
[1] Journal of the Indian Chemical Society, 1946, vol. 23, p. 427,428[2] Journal of the University of Bombay, Science: Physical Sciences, Mathematics, Biological Sciences and Medicine, 1946, vol. 15/3 A, p. 21,22
With diethylzinc; tris-(o-tolyl)phosphine;palladium diacetate; In 1-methyl-pyrrolidin-2-one; hexane; at 60℃; for 19.0h;
A solution of Pd(OAc)2 (0.012 g, 0.054 mmol) and tri-o-tolylphosphine (0.073 g, 0.240 mmol) in degassed N-methylpyrrolidone (2 mL) is heated at 60° C. for 30 minutes. A solution of 1.0 M diethylzinc in hexane (0.11 mL, 0.11 mmol) is then added and stirring is continued for additional 30 minutes. To this mixture is added a mixture of <strong>[1013-83-8]5-bromo-naphthalene-2-carboxylic acid</strong>, 1, (0.135 g, 0.536 mmol) and Zn(CN)2 (0.063 g, 0.536 mmol) in degassed N-methylpyrrolidone (2 mL). The resulting mixture is heated at 60° C. for 18 hrs. The reaction mixture is cooled and directly loaded to a prep-HPLC column eluting with CH3CN-H2O (0.1percent TFA) to afford 0.085 g (80percent yield) of the desired product as a white solid. m.p. 250° C. (dec.). 1H NMR (300 MHz, CDCl3): delta 8.61 (s, 1H), 8.18 (m, 2H), 8.14 (d, J=8.7 Hz, 1H), 7.94 (d, J=7.2 Hz, 1H), 7.54 (t, J=8.4 Hz, 1H). 13C NMR (75 MHz, CDCl3): delta 168.4, 134.9, 134.8, 134.5, 132.4, 131.9, 129.9, 128.5, 125.9, 125.5, 117.5, 110.2.
With methanol; thionyl chloride; at 25℃; for 4.0h;Heating / reflux;
5-Bromo-2-naphthoic acid (17.33 g, 69 mmol) and 250 mL of MeOH were combined in a flask under N2 atmosphere. Thionyl chloride (5.84 mL, 80 mmol) was added dropwise over 15 minutes at a temperature of 25-30 C. resulting in a pale yellow mixture. The mixture was heated at reflux for 3? hours. The resulting yellow solution was concentrated in vacuo to 137.4 g of solution then placed in the freezer overnight. The resulting thick mixture was filtered and the solid was washed with 100 mL of cold MeOH. The solid was dried in vacuo at 50 C. to give 11.39 g of intermediate title compound as white crystals. A second crop was filtered and washed with 100 mL of cold MeOH. The solid was dried to 1.31 g of white crystals. Yield: 69percent, 2 crops.
(Step 1) Preparation of 5-Bromo-2-hydroxymethylnaphthalene To a stirred solution of <strong>[1013-83-8]5-bromonaphthalene-2-carboxylic acid</strong> (10.04 g, 40 mmol) in dry THF (400 mL) cooled to 0° C. was added BH3 *THF (54 mL, 54 mmol; 1.0M solution in THF) dropwise over 45 minutes. The resulting solution was stirred overnight while warming to room temperature. The excess BH3 was quenched by the addition of H2 O (200 mL) at 0° C. and the volatiles were removed in vacuo. The aqueous residue was extracted with Et2 O (2*250 mL) and the combined organic layers were dried (MgSO4) and concentrated in vacuo to give the title compound as a colorless liquid which solidified to a white solid upon standing (9.48 g, 100percent). This material was of adequate purity to be used as such in the next step. NMR (200 MHz, CDCl3): delta 8.10 (d, 1H, J=8 Hz), 7.70 (m, 3H), 7.45 (dd, 1H, J=8,2 Hz), 7.25 (t, 7H, J=8 Hz), 4.75 (s, 2H), 2.55 (br s, 1H).
N-[(5-bromo-2-naphthalenyl)thioxomethyl]-N-methylglycine methyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
For example, by using <strong>[1013-83-8]5-bromo-2-naphthalenecarboxylic acid</strong>, described by H. Goldstein et al., Helv. Chim. Acta, 21, 62 (1938), as the starting material of formula II and following serially the procedures, N-[(5-bromo-2-naphthalenyl)thioxomethyl]-N-methylglycine methyl ester is obtained via the intermediate N-[(5-bromo-2-naphthalenyl)carbonyl]-N-methyl glycine methyl ester.
With hydrogenchloride; diisobutylaluminium hydride; In toluene;
B. 2-Bromo-5-(hydroxymethyl)-naphthalene A 42 g (0.167 mole) portion of <strong>[1013-83-8]5-bromo-2-naphthoic acid</strong> in 460 ml of toluene was treated with 460 ml (0.58 mole) of diisobutylaluminum hydride over 0.4 hours at 20°-25° with rapid stirring. The reaction mixture was then allowed to stand for 1 hour at ambient temperature, heated slowly to reflux over 0.5 hours, refluxed for 0.5 hours, allowed to cool slowly to room temperature and allowed to stand overnight at room temperature with stirring. The reaction mixture was then treated at 25°-30° with 36 ml of 1:1 H2 O-methanol, 18 ml of concentrated HCl and 200 ml of H2 O. The organic layer was separated, dried over MgSO4, filtered and concentrated under reduced pressure to give 39.5 g (97percent) of a light yellow oil which crystallized, m.p. 72°-75°. Further extraction of the aqueous phase with 300 ml of toluene gave an additional 1.0 g (3percent) of the desired product, m.p. 71°-75°.
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; acetonitrile; for 22.0h;Heating / reflux;
A mixture of 5-bromo-2-:naphthoic acid (2,12g, 8.44mmol), 1-methyl-4-(4,4,5,5- tetramethy1-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.84g, 8.86mmol), and tetrakis(triphenylphosphine p)alladium (0) (502mg, 0.435mmol) in a 250mL round bottomed flask was evacuated and purged with nitrogen (in three cycles). Acetonitrile (40mL) and 2M aqueous sodium carbonate (10mL) were added to the mixture via syringe, and the mixture was heated under reflux under nitrogen for 22 hours. The reaction mixture was allowed to cool before the addition of IM aqueous hydrochloric acid (30mL) and it was then extracted with ethyl acetate (3 x 50mL). The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo to provide a crude product (2.98g after air drying). This crude material was dissolved in hot ethanol (150mL) and filtered while hot to remove a yellow impurity (120mg). The filtrate was concentrated in vacuo and the residue was recrystallised from dichloromethane (30mL) to provide S-(1-methyl-1H-pyrazol-4-yl)-2-naphthoic acid as a white solid (724mg, 34percent). A second crop of 5-(1-methyil-1H-pyrazol-4-yl)-2-naphthoic acid (527mg, 25percent) was obtained from the concentrated mother liquors by recrystallisation from dichloromethane (2OmL).
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In acetonitrile; for 22.0h;Inert atmosphere; Reflux;
[0099] A mixture of <strong>[1013-83-8]5-bromo-2-naphthoic acid</strong> (2.12g, 8.44mmol), 1-methyl-4-(4,4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)- 7/-/-pyrazole (1.84g, 8.86mmol), and (0127) tetrakis(triphenylphosphine)palladium(0) (502mg, 0.435mmol) in a 250ml_ round bottomed flask was evacuated and purged with nitrogen (in three cycles). Acetonitrile (40ml_) and 2M aqueous sodium carbonate (10ml_) were added to the mixture via syringe, and the mixture was heated under reflux under nitrogen for 22 hours. The reaction mixture was allowed to cool before the addition of 1 M aqueous hydrochloric acid (30ml_) and it was then extracted with ethyl acetate (3 x 50ml_). The combined organic layers were dried (MgSCU), filtered, and concentrated in vacuo to provide a crude product (2.98g after air drying). This crude material was dissolved in hot ethanol (150ml_) and filtered while hot to remove a yellow impurity (120mg). The filtrate was concentrated in vacuo and the residue was recrystallised from dichloromethane (30ml_) to provide 5-(1-methyl-1 /--pyrazol-4-yl)-2-naphthoic acid as a white solid (724mg, 34percent). A second crop of 5-(1-methyl-1 /--pyrazol-4-yl)-2-naphthoic acid (527mg, 25percent) was obtained from the concentrated mother liquors by recrystallisation from (0128) dichloromethane (20ml_).
a) 5-Bromo-2-naphthonitrile To a solution of <strong>[1013-83-8]5-bromo-2-naphthoic acid</strong> (4.3 g, 17 mmol)) in dry pyridine (75 mL) at 0° C. was added methanesulfonyl chloride (1.4 mL, 18 mmol). After stirring at 0° C. for 1 h, ammonia gas was bubbled through the solution for 10 min, whilst maintaining the temperature below 5° C. During the gas addition the solution became viscous, so additional dry pyridine (~30 mL) was added. Excess ammonia was removed in vacuo, the solution again cooled to 0° C., then treated with additional methanesulfonyl chloride (12.5 mL) and allowed to warm to room temperature overnight. The solution was poured onto ice cold water, the mixture stirred for 30 min and the brown precipitate collected by filtration, washed on the sinter with ice cold water, then dried in vacuo. The crude product was dissolved in hot chloroform (~35 mL) and insoluble material filtered off. The chloroform was removed and the residue dissolved in a minimum volume of ether at reflux. Hexane was added until the solution remained turbid at reflux, the solution filtered rapidly into a pre-heated flask, and allowed to cool slowly to room temperature. The precipitate was collected by filtration, washed with hexane, and dried in vacuo, to yield 5-bromo-2-naphthonitrile. Further crops were obtained by cooling the filtrate at -18° C. overnight.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
