2-bromo-5-hydroxybenzoic acid

2-Bromo-5-methoxybenzoic acid5 g (manufactured by Wako Pure Chemical Industries, Ltd.) and 15 g of aluminum chloride were refluxed in 150 mL of chlorobenzene for 2.5 hours.After cooling, the reaction solution was transferred to ice water and extracted three times with 250 mL of diethyl ether. The obtained extract was concentrated under reduced pressure, diethyl ether was distilled off, 4.2 g of 2-bromo-5-hydroxybenzoic acid was obtained.3.9 g of the obtained 2-bromo-5-hydroxybenzoic acid and 3.9 g of resorcinol (Tokyo Chemical Industry Co., Ltd.) were dissolved in 9 mL of 4 M NaOH aqueous solution at 60 ° C., And heated for 30 minutes. To this reaction solution was added 1.8 mL of a 10percent aqueous solution of copper sulfate, Further, Heating was carried out for 10 minutes.The precipitate formed was collected by filtration, A white powder of urolitin A was obtained.5g of 2-bromo-5-methoxybenzoic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and 15 g of aluminum chloride were refluxed in 150 mL of chlorobenzene for 2.5 hours. After cooling, the reaction solution was transferred to ice water and extracted three times with 250 mL of diethyl ether. The obtained extract was concentrated under reduced pressure and diethyl ether was distilled off to obtain 4.2 g of 2-bromo-5-hydroxybenzoic acid. 3.9 g of the obtained 2-bromo-5-hydroxybenzoic acid and 3.9 g of resorcinol (Tokyo Chemical Industry Co., Ltd.) were heated in 9 mL of 4 M NaOH aqueous solution at 60 ° C. for 30 minutes. 1.8 mL of a 10percent aqueous solution of copper sulfate was added to the reaction solution, followed by further heating at 80 ° C. for 10 minutes. The precipitate formed was recovered by filtration to obtain a white powder of urolitin A.5 g of 2-bromo-5-methoxybenzoic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and 15 g of aluminum chloride were refluxed in 150 mL of chlorobenzene for 2.5 hours.After cooling, The reaction solution was transferred to ice water, Extraction was carried out three times with 250 mL of diethyl ether.The obtained extract was concentrated under reduced pressure, diethyl ether was distilled off, 4.2 g of 2-bromo-5-hydroxybenzoic acid was obtained.5 g of 2-bromo-5-methoxybenzoic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and 15 g of aluminum chloride were refluxed in 150 mL of chlorobenzene for 2.5 hours.After cooling, the reaction solution was transferred to ice water and extracted three times with 250 mL of diethyl ether. The obtained extract was concentrated under reduced pressure and diethyl ether was distilled off to obtain 4.2 g of 2-bromo-5-hydroxybenzoic acid. 3.9 g of the obtained 2-bromo-5-hydroxybenzoic acid and 3.9 g of resorcinol (Tokyo Chemical Industry Co., Ltd.) were heated in 9 mL of 4 M NaOH aqueous solution at 60 ° C. for 30 minutes. 1.8 mL of a 10percent aqueous solution of copper sulfate was added to the reaction solution, followed by further heating at 80 ° C. for 10 minutes. The precipitate formed was recovered by filtration, and urineA white powder was obtained.5 g of 2-bromo-5-methoxybenzoic acid (manufactured by Wako Pure Chemical Industries, Ltd.)And 15 g of aluminum chloride were refluxed in 150 mL of chlorobenzene for 2.5 hours. After cooling, the reaction solution was transferred to ice water, Extraction was carried out three times using 250 mL of diethyl ether.The obtained extract was concentrated under reduced pressure, diethyl ether was distilled off, 4.2 g of 2-bromo-5-hydroxybenzoic acid was obtained.3.9 g of the obtained 2-bromo-5-hydroxybenzoic acid and resorcinol3.9 g (manufactured by Tokyo Chemical Industry Co., Ltd.) was heated in 9 mL of 4 M NaOH aqueous solution at 60 ° C. for 30 minutes.1.8 mL of a 10percent aqueous solution of copper sulfate was added to the reaction solution, and further 80 ° C., Heating was carried out for 10 minutes. The precipitate formed was collected by filtration, A white powder of Urolithin A was obtained.Urolithins A and B were synthesized by Cun-mediated coupling of 1, 3- dihydroxybenzene and 2-bromo- 5-hydroxybenzoic acid (urolithin A) or 2-bromobenzoic acid (urolithin B) in concentrated aqueous NaOH according to already reported procedures (Bialonska D. et al., 20092Urolithins A and B were synthesized by CuII-mediated coupling of 1, 3-dihydroxybenzene and 2-bromo- 5-hydroxybenzoic acid (urolithin A) or 2-bromobenzoic acid (urolithin B) in concentrated aqueous NaOH according to already reported procedures (Bialonska D. et al., 20092-Bromo-5-hydroxybenzoic acid was obtained from commercially available 2-bromo-5-methoxybenzoic acid through demethylation by BBr3 (3 equiv.) in CH2Cl2/hexane (3:2, v/v) at low temperature (-20 to 0 C). Urolithins were isolated by precipitation and their purity checked by HPLC analysis. Their NMR and MS characteristics were in agreement with the literature. Urolithin C and D were purchased from Dalton Pharma Services (Toronto, Canada) and the certificates of analysis are available. Other compounds were commercially available.2-Bromo-5-methoxybenzoic acid5 g (manufactured by Wako Pure Chemical Industries, Ltd.) and 15 g of aluminum chloride were refluxed in 150 mL of chlorobenzene for 2.5 hours.After cooling, the reaction solution was transferred to ice water and extracted three times with 250 mL of diethyl ether. The obtained extract was concentrated under reduced pressure, diethyl ether was distilled off, 4.2 g of 5 g of 2-bromo-5-methoxybenzoic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and 15 g of aluminum chloride were refluxed in 150 mL of chlorobenzene for 2.5 hours. After cooling, the reaction solution was transferred to ice water and extracted three times with 250 mL of diethyl ether. The obtained extract was concentrated under reduced pressure and diethyl ether was distilled off to obtain 4.2 g of 3.9 g of the obtained In a 500 ml round bottom flask, a solution of 2-bromo-5-methoxy benzoic acid (10gm, 0.043moles) and AlCl3 (17.26 gm, 0.129 moles) in chlorobenzene (230 ml) was added and the reactionwas refluxed for 16 hrs at 131C. The product obtained was extracted using ethylacetateand concentrated using rotary evaporator. In a two necked round bottom flask, the demethylatedproduct (2-bromo-5-hydroxy benzoic acid) obtained in reaction 1 (8.7 gms, 0.04 moles)along with resorcinol (4.414 gm, 0.04 moles), sodium hydroxide (4 gm, 0.10 moles) was mixedwith water (45.5 ml) and reaction was refluxed for 2 hrs at 100C. To the above mixture, 10%w/v CuSO4 (17 ml) was added and refluxed for another 2 hrs. Crude product was purified bycolumn chromatography. The desired compound was eluted with a solvent mixture of hexane:ethyacetate (50:50) followed by recrystallization in ethylacetate to ensure high purity. The purifiedUA (1 g) was concentrated and characterized by TLC, NMR spectroscopy, mass spectroscopyand HPLC (S1 Scheme).5 g of 2-bromo-5-methoxybenzoic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and 15 g of aluminum chloride were refluxed in 150 mL of chlorobenzene for 2.5 hours.After cooling, the reaction solution was transferred to ice water and extracted three times with 250 mL of diethyl ether. The obtained extract was concentrated under reduced pressure and diethyl ether was distilled off to obtain 4.2 g of 5 g of 2-bromo-5-methoxybenzoic acid (manufactured by Wako Pure Chemical Industries, Ltd.)And 15 g of aluminum chloride were refluxed in 150 mL of chlorobenzene for 2.5 hours. After cooling, the reaction solution was transferred to ice water, Extraction was carried out three times using 250 mL of diethyl ether.The obtained extract was concentrated under reduced pressure, diethyl ether was distilled off, 4.2 g of In 150 mL of chlorobenzene, 5 g of 2-bromo-5-methoxybenzoic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and 15 g of aluminum chloride were refluxed for 2.5 hours. After cooling, the reaction liquid was transferred to ice water, and extraction was carried out using 250 mL of diethyl ether three times. The obtained extract was concentrated under reduced pressure to evaporate diethyl ether, to obtain 4.2 g of 1. To a reactor (Reactor 2), charge Resorcinol (4.00 eq.) and WFI (7 vol.) under N2. 2. Bubble the solution with N2. 3. Charge 50% aq. NaOH-2 (3.30 equiv.) and CuSO4 5H2O (0.0010 equiv.). 4. Bubble the solution with N2. 5. Polish filter the solution obtained above to a particulate-cleaned and N2-purged reactor (Reactor 3). 6. Wash/rinse the flask/lines with WFI water (3 vol.) 7. Heat the solution in Reactor 3 to 75±5 C. 8. Through a polish filter, slowly charge a pre-prepared solution of EXAMPLE 28 Preparation of 2-Bromo-5-hydroxybenzoic acid STR77 A mixture of 2-bromo-5-methoxybenzoic acid (10 g, 0.043 mol) in methylene chloride is cooled to -60 C., treated with boron tribromide (3.59 g, 0.143 mol), stirred at -60 C. for 1 hour, stirred at room temperature for 1 hour, cooled to -70 C., treated with additional boron tribromide (3.59 g, 0.143 mol), stirred at -70 C. for 1 hour, stirred at room temperature for 1 hour and poured into water. The aqueous mixture is extracted with ethyl acetate. The organic extracts are combined, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give the title product as a white solid which is identified by 1 H and 13 C-NMR spectral analyses.2-Bromo-5-hydroxybenzoic acid was obtained from commercially available 2-bromo-5- methoxybenzoic acid through demethylation by BBr3 (3 equiv.) in CE Cyhexane (3:2, v/v) at low temperature (-20 to 0 C).Urolithins A and B were synthesized by CuII-mediated coupling of 1, 3-dihydroxybenzene and 2-bromo- 5-hydroxybenzoic acid (urolithin A) or 2-bromobenzoic acid (urolithin B) in concentrated aqueous NaOH according to already reported procedures (Bialonska D. et al., 20092-Bromo-5-hydroxybenzoic acid was obtained from commercially available 2-bromo-5-methoxybenzoic acid through demethylation by BBr3 (3 equiv.) in CH2Cl2/hexane (3:2, v/v) at low temperature (-20 to 0 C). Urolithins were isolated by precipitation and their purity checked by HPLC analysis. Their NMR and MS characteristics were in agreement with the literature. Urolithin C and D were purchased from Dalton Pharma Services (Toronto, Canada) and the certificates of analysis are available. Other compounds were commercially available.2-Bromo-5-methoxybenzoic acid5 g (manufactured by Wako Pure Chemical Industries, Ltd.) and 15 g of aluminum chloride were refluxed in 150 mL of chlorobenzene for 2.5 hours.After cooling, the reaction solution was transferred to ice water and extracted three times with 250 mL of diethyl ether. The obtained extract was concentrated under reduced pressure, diethyl ether was distilled off, 4.2 g of 5g of 2-bromo-5-methoxybenzoic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and 15 g of aluminum chloride were refluxed in 150 mL of chlorobenzene for 2.5 hours. After cooling, the reaction solution was transferred to ice water and extracted three times with 250 mL of diethyl ether. The obtained extract was concentrated under reduced pressure and diethyl ether was distilled off to obtain 4.2 g of 5 g of 2-bromo-5-methoxybenzoic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and 15 g of aluminum chloride were refluxed in 150 mL of chlorobenzene for 2.5 hours.After cooling, The reaction solution was transferred to ice water, Extraction was carried out three times with 250 mL of diethyl ether.The obtained extract was concentrated under reduced pressure, diethyl ether was distilled off, 4.2 g of In a 500 ml round bottom flask, a solution of 2-bromo-5-methoxy benzoic acid (10gm, 0.043moles) and AlCl3 (17.26 gm, 0.129 moles) in chlorobenzene (230 ml) was added and the reactionwas refluxed for 16 hrs at 131C. The product obtained was extracted using ethylacetateand concentrated using rotary evaporator. In a two necked round bottom flask, the demethylatedproduct (2-bromo-5-hydroxy benzoic acid) obtained in reaction 1 (8.7 gms, 0.04 moles)along with resorcinol (4.414 gm, 0.04 moles), sodium hydroxide (4 gm, 0.10 moles) was mixedwith water (45.5 ml) and reaction was refluxed for 2 hrs at 100C. To the above mixture, 10%w/v CuSO4 (17 ml) was added and refluxed for another 2 hrs. Crude product was purified bycolumn chromatography. The desired compound was eluted with a solvent mixture of hexane:ethyacetate (50:50) followed by recrystallization in ethylacetate to ensure high purity. The purifiedUA (1 g) was concentrated and characterized by TLC, NMR spectroscopy, mass spectroscopyand HPLC (S1 Scheme).5 g of 2-bromo-5-methoxybenzoic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and 15 g of aluminum chloride were refluxed in 150 mL of chlorobenzene for 2.5 hours.After cooling, the reaction solution was transferred to ice water and extracted three times with 250 mL of diethyl ether. The obtained extract was concentrated under reduced pressure and diethyl ether was distilled off to obtain 4.2 g of 5 g of 2-bromo-5-methoxybenzoic acid (manufactured by Wako Pure Chemical Industries, Ltd.)And 15 g of aluminum chloride were refluxed in 150 mL of chlorobenzene for 2.5 hours. After cooling, the reaction solution was transferred to ice water, Extraction was carried out three times using 250 mL of diethyl ether.The obtained extract was concentrated under reduced pressure, diethyl ether was distilled off, 4.2 g of In 150 mL of chlorobenzene, 5 g of 2-bromo-5-methoxybenzoic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and 15 g of aluminum chloride were refluxed for 2.5 hours. After cooling, the reaction liquid was transferred to ice water, and extraction was carried out using 250 mL of diethyl ether three times. The obtained extract was concentrated under reduced pressure to evaporate diethyl ether, to obtain 4.2 g of General procedure: The title compounds synthesized within this study is shown inScheme 2 with the synthetic scheme.For the synthesis of UA, UB, and HMUA, a mixture of correspondingbenzoic acid derivative (2.3 mmol) and resorcinol(13.8 mmol) in sodium hydroxide aqueous solution (16.8 mmol, 25 mL) was heated for 1 h under reflux. Then, aqueous CuSO4(28%, 15 mL) was added to the reaction mixture. The precipitatedproduct was cooled, filtered, and washed with ice water.

Molecular Weight:217.02
XLogP3:2.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:215.94221
Monoisotopic Mass:215.94221
Topological Polar Surface Area:57.5
Heavy Atom Count:11
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes