3-HYDROXY-PYRIDINE-2-CARBOXYLIC ACID METHYL ESTER

To a suspension of 3-hydroxypicolinic acid 1 (10 g, 72 mmol, 1equiv) in methanol (150 mL, 0.5 M) was added dropwise at 0 °C aconcentrated sulfuric acid (12 mL, 216 mmol, 3 equiv.). The obtainedsolution was stirred at reflux 6 h. The cooled reaction mixture wasconcentrated under reduced pressure. The pH was adjusted at 8.5 withan aqueous solution of saturated NaHCOTo a stirred mixture of 3-thydroxypicolinic acid (10 g, 71.9 mmol) in 350 mL CHTo a solution of compound 20A (100.0 g, 0.719 mol, 1.0 eq) in methanol (1.5 L) was added cone, sulfuric acid (120 mL, 2.157 mol, 3.0 eq) and the reaction mixture was heated to reflux (83 °C) overnight. The solvent was removed in vacuo, and the residue was diluted with water (1.5 L), and adjusted to pH 8.5 with solid K2CO3-Hydroxypicolinic acid (5.0 g, 35.94 mmol) was dissolved in methanol (120 mL). A solution of 3-hydroxypicolinic acid (30 g, 0.22 mol) in CHHA mixture of 3-hydroxypicolinic acid (2 g, 14.1 mmol) in MeOH (100 mL) containing concentrated HIn 500mL single-neck flask fitted with a water separator, were added sequentially 4. 17g namely 0. 03mol 3-hydroxy-2-pyridine carboxylic acid, 350mL of anhydrous methanol, and then slowly added dropwise 6mL of concentrated sulfuric acid and 10mL benzene, under a nitrogen blanket reflux 24h. The reaction was stopped, cooled to room temperature, spin most methanol, with sodium hydroxide solution 2mol / L pH is adjusted to 4. 0~5. 0, extracted three times with 30mL dichloromethane and the combined organic phase was dried over anhydrous magnesium dried overnight, filtered, and the solvent under reduced pressure to spin, to give an off-white solid was dried in vacuo to give product 3. 0g, 65percent yieldReference 4- (6-formγl-5-methoxγpγridin-2-γl) benzonitrile; (step 1); A solution of 3-hydroxypicolinic acid (50.9 g) and cone, sulfuric acid (40 iαL) in methanol (500 mL) was heated under reflux for 5 days. The reaction mixture was concentrated under reduced pressure, and the residue was poured into cold water. The mixture was basified with potassium carbonate, and extracted twice with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (solvent gradient; 0-50percent ethyl acetate/hexane) and crystallized from ethyl acetate/hexane to give methyl 3-hydroxypyridine-2- carboxylate (35.5 g, 64percent) as white crystals.A mixture of 3-hydroxypicolic acid (1.39 g, 10.0 mmol) and HCl (2 M in methanol, 60 ml) was refluxed for 6 hours. The solvent was removed under reduced pressure and the residue was neutralized with saturated aqueous NaHCOIn a 500 ml_ round-bottorned flask fitted with a condenser-and a magnetic stirrer were placed MeOH (250 mL), S-hydroxypyridine^-carboxylic acid 1 (10.0 g, 72 mmol) and concentrated H^SO3-hydroxy picolinic acid (1.0 g, 7.19 mmol) in methanol (15 ml) solution was added dropwise concentrated sulfuric acid (200 μl). Under an argon atmosphere, and stirred under reflux conditions overnight. After completion of the reaction, concentrated to dryness. Saturated saline, a saturated aqueous solution of sodium hydrogen carbonate was added, and the mixture was extracted with chloroform. Dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. To give the title compound (250 mg, 23percent).Step 1

Molecular Weight:153.14
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:153.042593085
Monoisotopic Mass:153.042593085
Topological Polar Surface Area:59.4
Heavy Atom Count:11
Complexity:149
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes