5-Chloro-2-hydroxynicotinic acid

Sodium hypochlorite (14 percent available chlorine, 35 mL, 82.21 mmol) solution was added to a stirred solution of 2-hydroxynicotinic acid (7 g, 50. 3 mmol) in 10 percent aqueous NaOH solution. The solution was stirred for 48 h at room temperature. An aqueous solution of sodium sulfite (3.150g, 25 mmol) was added and further stirred for 30 min at room temperature. The solution was diluted by cold water and pH was adjusted to 2 by cold dilute HCI. The solids formed were filtered, washed by cold water and dried to yield 6.8 g (78 percent) OF 5-CHLORO-2-HYDROXY-NICOTINIC acid (70) as white solids. MP: 276 °C ; 1H-NMR (DMSO-d6): d 8.23 (d, J= 2.8 Hz, 1H), 8.29 (d, J= 2.8 Hz, 1H); EIMS : 174 (M+1).EXAMPLE 3 EXAMPLE 5 EXAMPLE 6 A suspension of 5-chloro-2-hydroxy-nicotinic acid (70) (6 g, 3.46 mmol) in thionyl chloride (200 mL) and DMF (1 mL) was refluxed for 3 h to yield a clear solution. The solution was cooled and the excess thionyl chloride was evaporated under vacuum. The residue was cooled in an ice bath and cold anhydrous methanol was added slowly. After stirring 15 min at 0 C, the solution was refluxed for 1 h under argon. The solution was cooled and the solvent was removed under vacuum. The residue was dissolved in ethyl acetate and washed subsequently by saturated NAHCO3 solution, water and brine. The organic phase was dried over MGS04 and evaporated to yield 4.3 g (60 %) of 2, 5-dichloro-nicotinic acid methyl ester (71) as colorless viscous OIL. IH-NMR (DMSO-d6): d 3.88 (s, 3H), 8.39 (d, J= 2.8 Hz, 1H), 8. 70 (d, J= 2.8 Hz, 1H) ; EIMS M/Z 206 (M).EXAMPLE 141 5-chloro-3-[(3-methyl-1-piperidinyl)carbonyl]-2-pyridinol The desired product was prepared by substituting Example 25 N-[2-Chloro-5-(trifluoromethyl)phenyl]-5-chloro-2-hydroxynicotinamide (Comopund No. 25). Using EXAMPLE 5 5-Chloro-2-hydroxy-3-pyridinecarboxylic acid To an agitated solution of 216.0 g of sodium hydroxide pellets in 2.25 liters of 5% (1.51 moles) sodium hypochlorite solution was added 150.1 g (1.08 mole) of 2-hydroxynicotinic acid. Temperature of the reaction mixture was 20 C. Four hours later 750 ml of 5% (0.50 mole) of sodium hypochlorite solution was added and stirring was continued overnight. The reaction mixture was mixed with 12N hydrochloric acid in an agitated vessel in such a manner that the receiving solution was always strongly acid and temperature was kept below 20 C. with an ice bath. The amount of 12N acid used was 600 ml. The mixture was readily filtered on a sintered glass suction funnel. The crystalline filter cake was washed with 800 ml of water followed by 800 ml of 1:1 isopropyl ether/isopropyl alcohol. Crystals were powdery when dry. The weight of dry crystals was 153.2 g (81.8% yield). Analysis by 1 H-NMR showed the dried product contained no starting material and contained about 5% of 3, 5-dichloro-2-hydroxypyridine. See Example 3 for method of computing impurity.EXAMPLE 6 5-Chloro-2-hydroxy-3-pyridinecarboxylic acid To an agitated solution of 216.0 g of sodium hydroxide pellets in 2.25 liters of 5% (1.51 moles) of sodium hypochlorite solution was added 150.4 g of 2-hydroxynicotinic acid. Temperature of the reaction mixture was 19 C. Three hours later 750 ml (0.50 mole) of sodium hypochlorite was added and stirring was continued overnight. The reaction mixture was mixed with 12N hydrochloric acid in an agitated vessel in such a manner that the receiving solution was always strongly acid and temperature was kept below 20 C. with an ice bath. The amount of 12N acid used was 600 ml. The mixture was readily filtered on a sintered glass suction funnel. The crystalline filter cake was washed with 600 ml of water followed by 800 ml of 1:1 isopropyl ether/isopropyl alcohol. Weight of the dry crystals was 143.5 g (76.6% yield). Analysis by 1 H-NMR analysis showed the dried product contained no starting material and about 5% 3, 5 -dichloro-2-hydroxypyridine. See Example 3 for method of computing impurity.To a suspension of

Molecular Weight:173.55
XLogP3:0.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:172.9879707
Monoisotopic Mass:172.9879707
Topological Polar Surface Area:66.4
Heavy Atom Count:11
Complexity:280
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes