* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Stage B: ethyl 5-hydroxynicotinateTo 2.5 g (18 mmol) of compound prepared in stage A dissolved in 50 mL of ethanol and cooled to 00C was added carefully 4.4 mL (61 mmol) of thionyl chloride. The reaction mixture was then heated under reflux for 24 hours and then evaporated under reduce pressure. The crude product was poured into water and then filtered giving 2.5 g (yield: 83percent) of compound of molecular formula CsHgNOv Aspect: white powder.Melting point: 1500C.NMR spectrum of the protonIn OMSO-d6 at 300MHz, chemical shifts (ppm) and multiplicity: 8.74 (d, J = 1.2 Hz, IH), 8.60 (d, J = 2.6 Hz, 1 H), 8.07 (m, 1 H), 4.44 (q, J = 7.1 Hz, 2H), 1.42 (t, J = 7.1 Hz, 3H). EPO <DP n="117"/>Infrared spectrumIR spectrum was obtained as potassium bromide pellets. Absorption bands are given in cm"1:3044,2874,2677, 1731.
Reference：
[1] Patent: WO2006/103120, 2006, A2, . Location in patent: Page/Page column 115-116
[2] Patent: CN105418620, 2016, A, . Location in patent: Paragraph 0008; 0009
With sulfuric acid; nitric acid; at 0℃; for 48h;Heating;
At 0 C, to a solution of 5- hydroxypyridine-3-carboxylic acid (6.65 g, 47.80 mmol) in sulfuric acid (9 mL) was added HNO3 (12.60 g, 0.2 mol) dropwise. The resulting mixture was stirred for 48 h at 55 C. When the reaction was done, the reaction mixture was diluted with ice water (100 mL). The pH value of the mixture was adjusted to 5 with sodium hydroxide solution (5 M). The resulting mixture was extracted with isopropyl alcohol (200 mL x 3). The organic phases were combined and concentrated under reduced pressure to yield 5-hydroxy-6-nitropyridine-3-carboxylic acid as an yellow solid (8.00 g, 91 %).
64%
With sulfuric acid; nitric acid; at 55 - 60℃; for 96h;
1. 6-Nitro-5-hydroxynicotinic acid (B2): To a solution of 5-hydroxynicotinic acid (B1) (7.0 g, 50 mmol) in concentrated H2SO4 was added 9 mL of fuming HNO3 (90%) (9 mL). The reaction mixture was stirred at 55-60 C. in a sealed tube for four days. The mixture was then poured into ice and the pH was adjusted to 3 with 50% NaOH. MgSO4 was added to saturate the aqueous mixture, which was then extracted with isopropyl alcohol (4*45 mL). After the removal of isopropyl alcohol under reduced pressure, 5.93 g (64% yield) of B2 was obtained as a yellow solid. MS (APCI), (M+H)+185. 1H-NMR (DMSO-d6) delta 8.01 (d, 1H, Ar-H), 8.41(d, 1H, Ar-H).
64%
6-Nitro-5-hydroxynicotinic acid (B2): To a solution of 5-hydroxynicotinic acid (B1) (7.0 g, 50 mmol) in concentrated H2S04 was added 9 mL of fuming HN03 (90%) (9 mL), The reaction mixture was stirred at 55-60C in a sealed tube for four days. The mixture was then poured into ice and the pH was adjusted to 3 with 50% NaOH. MgS04 was added to saturate the aqueous mixture, which was then extracted with isopropyl alcohol (4x45 mL). After the removal of isopropyl alcohol under reduced pressure, 5.93 g (64% yield) of B2 was obtained as a yellow solid. MS (APCI), (M+H)+ 185. 1HNMR (DMSO-dQ)a 8.01 (d, 1H, Ar-H), 8.41 (d, 1H, Ar-H).
With sulfuric acid; nitric acid; at 0 - 20℃; for 16h;Sealed tube;
In a sealable tube, 5-hydroxypyridine-3-carboxylic acid (1.00 g, 5.95 mol) was dissolved in concentrated H2SO4 (1.34 mL). Then fuming nitric acid (1.35 mL) was added drop wise at 0-5 C and the reaction mixture brought to room temperature slowly and stirred for 16 hrs before being poured onto ice cold water. The pH was adjusted to 3 with 50% NaOH solution and then extracted with isopropyl alcohol: chloroform (1 :19, 4x45 mL). After separation of layers and removal of solvent under reduced pressure, a pale yellow solid was obtained (1.2 g), consisting of a mixture of starting material and 5-hydroxy-6- nitropyridine-3-carboxylic acid in a 2:3 ratio
43 g
With sulfuric acid; nitric acid; at 20 - 30℃; for 14h;
The 89.6 ml nitric acid (65% a) slowly added to 560 ml sulfuric acid (96% a) in, from the internal temperature does not exceed 30 C. Therefore, to divide at room temperature by adding 70g5-hydroxy nicotinic acid (CAS5006-66-6), and the mixture is stirred 14 hours. The mixture is poured into a large amount of ice water, and the obtained precipitate K1 leach. The filtrate is the use of aqueous sodium hydroxide solution to pH= 3, extracted with ethyl acetate 3 times. The combined organic phase is washed with water and dried with sodium sulfate. Remove the solvent in a vacuum. A residue by another K2. Merger of the two parts of the sediment, produce 43g5-hydroxy-6-nitro-pyridine-3-carboxylic acid.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
