With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.73406-50-5, name is Ethyl 3-hydroxypicolinate, molecular formula is C8H9NO3, molecular weight is 167.162, as common compound, the synthetic route is as follows.Formula: C8H9NO3
3-Hydroxy-picolinic acid (15.6 g, 42.1 mmol), ethanol (360 mL), benzene (100 mL) and 98% sulfuric acid (6 mL) were heated under reflux for 40 h. After evaporation of the ethanol and benzene, the residue was dissolved in water, neutralized with sodium bicarbonate, and extracted with chloroform. The organic layer was dried (MgS04), filtered, and then the solvent was evaporated to give ethyl 3-hydroxy-picolinate as a brown oily residue (11.0 g).A mixture of ethyl 3-hydroxy-picolinate (11.0 g, 65.8 mmol), ethyl bromoacetate (12.1 g, 72.4 mmol) and anhydrous potassium carbonate (11.8 g, 85.5 mmol) in acetone (120 mL) was heated under reflux for 15 h. After cooling, the inorganic material separated by filtration. The filtrate was dissolved in chloroform, washed with water, then brine and dried (MgSO4), filtered, and the solvent was evaporated to give a brown oily residue. The residue was purified by flash chromatography using a gradient of ammoniated methanol in chloroform to give ethyl 2- (2-ethoxycarbonyl-3-pyridyloxy) acetate (13.7 g) as a yellow oil (13.7 g). Ethyl 2- (2-ethoxycarbonyl-3-pyridyloxy) acetate (13.6 g, 54.0 mmol) and sodium ethoxide (8. 08 g, 118.8 mmol) in toluene (200 mL) were heated under reflux for 18 h. After cooling, a precipitate was collected by filtration, dissolved in the minimum amount of hot water (about 300 mL), and acidified with acetic acid (6 mL). The resulting precipitate was filtered, and dried in vacuo to give ethyl 3-hydroxyfuro [3,2-b] pyridine-2-carboxylate as a solid (7.0 g). Ethyl 3-hydroxyfuro [3,2-b] pyridine-2-carboxylate (6.90 g, 25.8 mmol) was dissolved in 10% hydrochloric acid (50 mL), and heated under reflux for 3 h. Evaporation of the hydrochloric acid solution gave furo [3,2-b] pyridin-3 (2H)-one hydrochloride (9.0 g). A portion of the furo [3,2-b] pyridin-3 (2H) -one hydrochloride was converted to its free base by treatment with saturated sodium bicarbonate and extraction with chloroform in preparation for the following step. N, N-Diisopropylethylamine (1.08 g, 8.34 mmol) was added slowly to a solution of furo [3,2-b] pyridin-3 (2H) -one (1.40 g, 7.25 mmol) in dry dichloromethane (60 mL) under nitrogen at-10°r; C. Then trifluromethanesulfonic anhydride (2.45 g, 8.70 mmol) was added slowly. The mixture was warmed to RT, and stirred overnight. The reaction was quenched with water. The organic layer was washed with water and brine, dried (MgS04), and then the solvent was evaporated to give a brown oily residue, which was purified by flash chromatography using chloroform to give the sub-title compound (980 mg) as a light-brown oil.
At the same time, in my other blogs, there are other synthetic methods of this type of compound,73406-50-5, Ethyl 3-hydroxypicolinate, and friends who are interested can also refer to it.
Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/42538; (2005); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem