Dimethyl 5-hydroxyisophthalate

off-white crystal powder

To a 1-L round-bottom flask equipped with a magnetic stirring bar were added 187.8 g (1 mol) of 5-hydroxyisophthalic acid commercially available from Aldrich (purity approximately 97percent) and 500 mL (12.3 mol) of methanol. After the addition of 28 mL of concentrated H2SO4, the mixture was heated to the reflux temperature and stirred under reflux for 4 hours. The hot solution was poured into 500 mL of ice water. Then, the white solid product was filtered off and washed on the filter with several portions of water until the pH of the wash liquid was neutral. The product was dried under vacuum, preferably at 60° C. overnight, to give 206.8 g of dimethyl 5-hydroxyisophthalate. Testing on the composition revealed the following data: mp 164-166° C.; GC purity >99percent; yield 98.2percent; 1H NMR (in CDCl3+DMSO-d6 W/TMS, ppm): 3.68 (s, 6H, OCH3), 7.45 (s, 2H, CH), 7.89 (s, 1H, CH), 9.35 (broad, 1H, OH); {1H}13C NMR (in CDCl3+DMSO-d6 w/TMS, ppm): 51.92 (OCH3), 120.50 (C4, C6), 121.10 (C2), 131.15 (C1, C3), 157.36 (C5), 165.85 (COOR); 1H-13C NMR (in CDCl3+DMSO-d6 w/TMS, ppm): 51.92 (quartet, OCH3, 1JCH=147 Hz), 120.50 (d, C4, C6, 1JCH=164.4 Hz), 121.10 (d, C2, 1JCH=168.3 Hz), 131.15 (s, C1, C3), 157.36 (s, C5), 165.85 (s, COOR); GC-MS (in acetone): 210 (M+).Into a 250 mL single-necked round bottom flask equipped with a magnetic stirring barand a reflux condenser were placed 5-hydroxyisophthalic acid (25 g, 13.72 x 102mol), methanol (125 mL) and sulfuric acid (lmL). The reaction mixture was heated at65 °C for 10 h. The excess methanol was removed on a rotary evaporator. The residue was dissolved in chloroform (125 mL) and the solution was washed with water (2 x 70 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and solvent was removed to obtain the crude product which was recrystallizedfrom methanol to afford pure dimethyl-5-hydroxyisophthalate.Yield: 98 percent; M.P. 162 °C; ‘H NIVIR (400 IVIHz, CDC13): ppm = 8.24 (s, 1H, Ar-H flanked by carbonyl), 7.77 (d, 2H, Ar-H, ortho to ether), 3.94 (s, 6H, -CH3).In the three-necked flask, followed by adding between 0.22mol5- hydroxy acid, 300ml of methanol and 12ml of concentrated sulfuric acid, The reaction was refluxed in an oil bath 70 deg c , TLC monitoring, the reaction was cooled to room temperature. The reaction solution was slowly added to distilled water to precipitate the heavy white precipitate, filtration, and dried in vacuo to afford a white powder in a yield of 96.8percent, 5-hydroxy acid intermediate product methyl ester, m.p. 169 .30 ml of concentrated sulphuric acid are added, dropwise, to a solution of 54.6 g (0.3 mol) of 5-hydroxyisophthalic acid in 500 ml of methanol. The reaction medium is heated under reflux for 24 hours. After evaporation, the residue is taken up in ethyl acetate and extracted with water. The organic phase is dried over anhydrous magnesium sulphate and then concentrated. The residue is triturated in heptane. [00237] White solid. m=59.8 g. Y=95percent. m.p.=162-4° C. Synthesis of Compound AConcentrated sulfuric acid (50 mL) was added to a solution of 5- hydroxyisophthalic acid (250 grams, 1.54 moles) in methanol (750 mL). The resulting solution was heated at reflux for 6 hours and then concentrated under reduced pressure of about 0.013-0.052 atmospheres. The resulting oily white solid was dissolved in ethyl acetate (500 mL) and washed consecutively with a saturated aqueous sodium bicarbonate solution, water, and then with a saturated sodium chloride solution. The resulting organic layer was dried over magnesium sulfate, filtered, and concentrated under reduced pressure of about 0.013-0.052 atmospheres. The residue was the desired diester Compound A (56 grams, 78 percent yield) with a melting point of 165-166 5-Hydroxyisophthalic acid (16.2 g, 89.0 mmol) was dispersed in 150 ml of methanol in an eggplant-shaped flask. The dispersion was combined with 3.0 ml of concentrated sulfuric acid, and the mixture was refluxed at 75°C for 3 hours and half. After the reaction, distilled water and a saturated aqueous solution of sodium hydrogencarbonate were added in excess. The precipitate formed was filtered off and dried under reduced pressure. The resultant solid was purified by recrystallization method using a hexane/chloroform mixed solvent to afford methyl 5-hydroxyisophthalate represented by the above formula (5) as a white solid (amount: 13.8 g, yield: 73.8percent). The compound structure was identified by the 1H-NMR spectrum given below: 1H-NMR, δ(400 MHz, CDCl3, ppm) : 3.87 (6H, s), 6.25 (1H, s), 7.64 (2H, d, J=1.47 Hz), 8.17 (1H, t, J=1.46 Hz).To a stirred solution of 5-hydroxyisophthalic acid (25 g, 137 mmol, 1 eq.) in 200 mL of methanol at room temperature, 2, 2-dimethoxypropane (1.2 eq.) and p-toluenesulfonic acid (TsOH, 0.2 eq.) were added. After stirring at 60° C., methanol was removed by evaporation. The resultant crude mixture was partitioned in ethyl acetate (EtOAc)/water. The organic layer was dried with magnesium sulfate (MgSO

Molecular Weight:210.18
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:4
Exact Mass:210.05282342
Monoisotopic Mass:210.05282342
Topological Polar Surface Area:72.8
Heavy Atom Count:15
Complexity:226
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes