* 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.
Reference：
[1] Chemical and Pharmaceutical Bulletin, 2005, vol. 53, # 12, p. 1540 - 1546
[2] Journal of Organic Chemistry, 1997, vol. 62, # 26, p. 9365 - 9368
[3] Journal of the American Chemical Society, 1984, vol. 106, # 11, p. 3297 - 3306
[4] Journal of the American Chemical Society, 1992, vol. 114, # 24, p. 9309 - 9317
[5] Chemische Berichte, 1922, vol. 55, p. 1854
[6] Bulletin of the Korean Chemical Society, 2011, vol. 32, # 5, p. 1475 - 1482
[7] Angewandte Chemie - International Edition, 2018, vol. 57, # 2, p. 465 - 469[8] Angew. Chem., 2018, vol. 130, # 2, p. 474 - 478,5
[9] Angewandte Chemie - International Edition, 2018, vol. 57, # 2, p. 465 - 469[10] Angew. Chem., 2018, vol. 130, # 2, p. 474 - 478,5
[11] Organic Letters, 2018, vol. 20, # 19, p. 6284 - 6288
2
[ 76635-70-6 ]
[ 20717-79-7 ]
Yield
Reaction Conditions
Operation in experiment
78.6%
With potassium permanganate In water; acetone for 5.5 h; Reflux
4) in a 250 ml round-bottom flask by adding 1.59g1-bromo-2-hydroxy methyl naphthalene and 22 ml acetone, heating to reflux. The 3.67g potassium permanganate dissolved in 8.1 ml water and 55 ml acetone, the add drop after heating thereof in the round-bottom flask, the 30 min, heat to reflux and 5h, the solution becomes brown, stop should be instead instead, filtering, the generated MnO2solid precipitate is filtered, washing with ethyl ether. Concentrated to obtain the product (1-bromo-2-naphthoic acid) 1.32g, the yield is 78.6percent.
Reference：
[1] Patent: CN105541605, 2016, A, . Location in patent: Paragraph 0017; 0026; 0035; 0044; 0071; 0080
[2] Journal of Organic Chemistry, 1983, vol. 48, # 21, p. 3869 - 3876
3
[ 2586-62-1 ]
[ 20717-79-7 ]
Reference：
[1] Chemische Berichte, 1987, vol. 120, p. 1151 - 1174
[2] Synthesis, 2000, # 12, p. 1677 - 1680
[3] Chemistry - A European Journal, 2015, vol. 21, # 19, p. 7030 - 7034
[4] Journal of Fluorine Chemistry, 1988, vol. 38, p. 139 - 152
[5] Chemical and Pharmaceutical Bulletin, 2005, vol. 53, # 12, p. 1540 - 1546
[6] Journal of the American Chemical Society, 1984, vol. 106, # 11, p. 3297 - 3306
[7] Journal of Organic Chemistry, 1983, vol. 48, # 21, p. 3869 - 3876
[8] Chemische Berichte, 1922, vol. 55, p. 1854
[9] Bulletin of the Korean Chemical Society, 2011, vol. 32, # 5, p. 1475 - 1482
[10] Journal of the American Chemical Society, 2014, vol. 136, # 36, p. 12784 - 12793
[11] Patent: CN105541605, 2016, A,
[12] Angewandte Chemie - International Edition, 2018, vol. 57, # 2, p. 465 - 469[13] Angew. Chem., 2018, vol. 130, # 2, p. 474 - 478,5
[14] Angewandte Chemie - International Edition, 2018, vol. 57, # 2, p. 465 - 469[15] Angew. Chem., 2018, vol. 130, # 2, p. 474 - 478,5
4
[ 37763-43-2 ]
[ 20717-79-7 ]
Reference：
[1] Journal of the American Chemical Society, 1984, vol. 106, # 11, p. 3297 - 3306
[2] Journal of Organic Chemistry, 1983, vol. 48, # 21, p. 3869 - 3876
[3] Chemische Berichte, 1922, vol. 55, p. 1854
[4] Patent: CN105541605, 2016, A,
5
[ 91-57-6 ]
[ 20717-79-7 ]
Reference：
[1] Journal of the American Chemical Society, 1984, vol. 106, # 11, p. 3297 - 3306
[2] Patent: CN105541605, 2016, A,
4.3 General procedure for the synthesis of methyl 2-haloarylcarboxylates 3a, 3b and 8
General procedure: The proper 2-haloarylcarboxylic acid (12mmol) was dissolved in 60mL of methanol and to this solution 8mL (12 equiv.) of concentrated sulfuric acid were then added dropwise. Then the reaction mixture was stirred at reflux until no more starting product was detected by TLC analysis. The reaction mixture was then cooled to rt and concentrated under reduced pressure. The residue was diluted with EtOAc (20mL) and washed with a saturated aqueous solution of NaHCO3 (3×30mL). The organic phase was dried over Na2SO4, filtered and the solvent was removed at reduced pressure to yield the corresponding methyl 2-haloarylcarboxylates.
95%
With sulfuric acid at 20℃; for 12h;
2 Example 2 Preparation of methyl 1-bromo-2-naphthalenecarboxylate
1-Bromo-2-naphthoic acid (9.00 g, 35.85 mmol)Soluble in 200ml of methanol,In addition, 20 ml of concentrated sulfuric acid was added dropwise to the reaction solution.After stirring for 12 hours at room temperature,The reaction was stopped, and the reaction mixture was quenched with water, extracted with dichloromethane and dried over anhydrous magnesium sulfate. The solution was concentrated to give a pale yellow solid which was purified by silica gel column chromatography.A petroleum ether/dichloromethane mixed solvent (5/1, v/v) was eluted to give a white solid with a yield of 95%.
95%
With sulfuric acid at 20℃; for 12h;
1.3
Compound M2 (9.00 g, 35.85 mmol) was dissolved in 200 mL of methanol, and 20 mL of concentrated sulfuric acid was added dropwise to the reaction solution. After stirring at room temperature for 12 hours, the reaction was stopped, the reaction was quenched with water, and dichloromethane was used. Extraction and drying were performed with anhydrous magnesium sulfate, and the solution was concentrated to obtain a khaki solid, which was purified by silica gel column chromatography to obtain a white solid with a yield of 95%.
92%
With thionyl chloride at -15 - 40℃; for 3.5h;
1.5
5) in a 50 ml round-bottom flask is added in 1 ml dry methanol, at -15 ° C lower, syringe by adding 0.2 ml new jeung of thionyl chloride. Then the 0.1g1-bromo-2-naphthalene carboxylic acid is dissolved in 2.5 ml dry methanol, at -15 ° C lower, 1 hour to four times its added to a methanol/thionyl chloride mixed solution. Slow heating to 40 °C, stirring for 2.5 hours. Stop the reaction, cooling to room temperature, for rotary evaporimeter removing excess methanol and thionyl chloride, the chromatographic column for of the crude product (CH2Cl2: petroleum ether = 1:1) separation and purification, to obtain white solid (1-bromo-2-naphthalene carboxylic acid methyl ester) 0.0975g, yield 92%.
89%
With sulfuric acid
85%
With sulfuric acid at 110℃; for 18h; Inert atmosphere;
1 Example 11-bromo-bisNaphthoic acid methyl esterOf the preparation The chemical reaction equation is as follows:
Under an argon atmosphere, 1-bromo-2-naphthoic acid (10 g, 39.83 mmol)Add two bottles, then add 100mL methanol,Then concentrated sulfuric acid (39.06 mg, 398.29 mol) was added dropwise,Heated to 110 ° C, reacted for 18 h; the reaction mixture was poured into water, Extracted with ethyl acetate, and the organic layer was completely washed with brine,Add anhydrous magnesium sulfate dry. The solution was concentrated to give the crude product as a white solidPurification by silica gel column chromatography (eluent selection petroleum ether / dichloromethane = 3/1, v / v)The product was left in the refrigerator for a long time to give a white solid in 85% yield.1H NMR, 13CNMR, MS and elemental analysis results show the resultingAs the target product.
85%
With sulfuric acid at 110℃; for 18h; Inert atmosphere;
1 Example 1Preparation of 1-Bromodinaphthalene Methyl Ester
1-bromo-2-naphthoic acid (10 g, 39.83 mmol) was added to a two-necked flask under an argon atmosphere,Then add 100mL methanol, and then by adding dropwise concentrated sulfuric acid (39.06mg, 398.29umol)Heated to 110 ° C, reacted for 18 h; the reaction mixture was pouredInto the water, extracted with ethyl acetate, the organic layer was washed thoroughly with brine and dried over anhydrous magnesium sulfate. After the solution was concentrated,The crude product was purified by silica gel column chromatography (eluent selection of petroleum ether / dichloromethane = 3/1, v / v) and the product was placedRefrigerator to give a white solid in 85% yield.
85%
With sulfuric acid at 110℃; for 18h; Inert atmosphere;
1 Example 11-bromo-2-naphthoic acid Methyl ester
Under an argon atmosphere,1-Bromo-2-naphthoic acid (10 g, 39.83 mmol)Add two bottles,Then add 100mL methanol,Then concentrated sulfuric acid (39.06 mg, 398.29 mol) was added dropwise,It was heated to 110 , reaction was 18h.The reaction mixture was poured into water,Extracted with ethyl acetate,After the organic layer was completely washed with brine,Add anhydrous magnesium sulfate dry.After the solution was concentrated,To obtain a crude product of white solid,And purified by silica gel column chromatography (Eluent selection of petroleum ether / dichloromethane = 3/1, v / v),The product is placed in a refrigerator for a long time to give a white solid,Yield 85%.
85%
With sulfuric acid at 110℃; for 18h; Inert atmosphere;
1 Example 1 1-bromo-2-naphthoic acid methyl ester
Under argon atmosphere, 1-bromo-2-naphthoic acid (10g, 39.83mmol) was added to the two-necked flask, then add 100mL methanol, then concentrated sulfuric acid (39.06 mg, 398.29 μmol) was added dropwise and heated to 110 °C. for 18 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed thoroughly with brine and then dried over anhydrous magnesium sulfate. The solution was concentrated to give a crude white solid which was purified by silica gel column chromatography (eluent petroleum ether / methylene chloride = 3/1, v/v). The product was left in the refrigerator for a long time to give a white solid with a yield of 85%.
85%
With sulfuric acid at 110℃; for 18h; Inert atmosphere;
2 Example 2Preparation of methyl 1-bromonaphthalene
1-Bromo-2-naphthoic acid (10 g, 39.83 mmol) was added to a two-neck flask under an argon atmosphere,An additional 100 mL of methanol was added, then concentrated sulfuric acid (39.06 mg, 398.29 μmol) was added dropwise and heated to 110 ° C.,The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed thoroughly with brine and dried over anhydrous magnesium sulfate. After the solution was concentrated, the crude product was obtained as a white solid which was purified by silica gel column chromatography The choice of petroleum ether / methylene chloride = 3/1, v / v), the product was placed in the refrigerator for a long time to give a white solid, a yield of 85%
85%
With sulfuric acid at 110℃; for 16h;
4.1.1. Synthesis of methyl 1-bromo-2-naphthoate (1)
Concentrated sulfuric acid (5.0 mL) was added dropwise into a solutionof 1-bromo-2-naphthoic acid (10 g, 39.83 mmol) and methanol(1.28 g, 39.83 mmol). The resulting mixture was heated to 110 °C for 16h and quenched with water. It was extracted with ethyl acetate, washedwith saturated saline, dried over anhydrous MgSO4 and then concentrated. The residue was purified by column chromatography onsilica gel with petroleum ether and ethyl acetate as eluents (5:1, v/v) togive a white solid in an 85% yield (8.94 g). 1H NMR (500 MHz, CDCl3) δ(ppm): 8.46 (m, 1H), 7.85 (m, 2H), 7.72-7.56 (m, 3H), 4.01 (s, 3H). MS(MALDI-TOF) m/z: calcd for C12H9BrO2 (M+), 263.98; found: 263.97.Anal. Calcd for C12H9BrO2: C, 54.37; H, 3.42%. found: C, 54.56; H,3.61%.
72%
With sulfuric acid at 65℃; for 16h;
53%
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride
With thionyl chloride
With thionyl chloride for 3h; Heating;
With sulfuric acid for 5h; Heating / reflux;
10.a
Example 10: 2-Methyl-2-[1 -(3-phenyl-propylamino)-naphthalene-2-carbonyl]-amino}- propionic acida) i-Bromo-naphthalene-2-carboxylic acid methyl esterTo 2.00 g 1-bromo-naphthalene-2-carboxylic acid in 20 ml of dry methanol 5 ml of sulfuric acid were added. After 5 h at reflux, the reaction was poured onto ice-water, and the precipitated product was collected by filtration and washed until neutral. After recrystallization from heptane 1.90 g i-bromo-naphthalene-2-carboxylic acid methyl ester were obtained.0-12HgBrO2 (265.11), NMR (400 MHz, CDCI3): δ [ppm] = 8.45 (d, 1 H), 7.85 (m, 2H),7.7 -7.55 (m, 3H), 4.0 (s, 3H).
With thionyl chloride
448.8 mg
With sulfuric acid Cooling with ice; Reflux;
Stage #1: 1-bromo-2-naphthoic acid With thionyl chloride In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere; Schlenk technique;
Stage #2: methanol In dichloromethane Inert atmosphere; Schlenk technique;
With thionyl chloride
10.8 g
With sulfuric acid at 20 - 80℃; for 4.5h;
(Synthesis of Intermediate 1)
After adding 10.7 g of 1-bromo-2-naphthoic acid to 100 mL of methanol, 27 mL of concentrated sulfuric acid was added dropwise with stirring at room temperature. The mixture was stirred in an oil bath at 80 ° C. for 4.5 hours.The reaction solution was returned to room temperature, the reaction solution was added little by little to about 300 mL of ice water, and then suction filtration was performed.The filtrate was dissolved in about 100 mL of dichloromethane, magnesium sulfate and white clay were added, and the mixture was stirred at room temperature.By filtering through silica gel and distilling off the solvent, 10.8 g of a white solid of Intermediate 1 was obtained.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
