Methyl 4-Hydroxyquinoline-2-carboxylate Chemical Properties

Melting point:

224 °C

Boiling point:

412.3±25.0 °C(Predicted)

Density 

1.327±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

pka

3.53±0.40(Predicted)

Appearance

Light brown to yellow Solid

Methyl 4-Hydroxyquinoline-2-carboxylate Usage And Synthesis

Uses

Methyl 4-Hydroxyquinoline-2-carboxylate is used in preparation of macro-heterocyclic compounds as blood coagulation factor XIa inhibitors.

Synthesis

4-Hydroxyquinoline-2-carboxylic acid (500 mg, 2.65 mmol) was suspended in anhydrous methanol and concentrated sulfuric acid (96%, 40 drops) was added slowly until the solution was clarified. The reaction mixture was heated to reflux and the reaction was kept at reflux for 24 hours (the progress of the reaction was monitored by LC-MS until the starting material disappeared completely). After completion of the reaction, it was cooled to room temperature. The solvent was removed using a rotary evaporator to give the crude product. The crude product was dissolved in methanol (1 mL) and diluted by adding deionized water (10 mL). Subsequently, saturated sodium bicarbonate solution was added slowly until a white precipitate precipitated. The precipitate was collected by filtration and washed with diethyl ether to give a white solid product in 65% yield (0.35 g). The product was characterized by 1H NMR (DMSO-d6, 500 MHz) and LC-MS (ES+): 1H NMR δ 3.52 (s, 3H), 6.48 (s, 1H), 7.25 (t, 1H, J = 7.0 Hz), 7.58 (t, 1H, J = 7.0 Hz), 7.96 (d, 1H, J = 8.5 Hz), 8.05 (d, 1H, J = 8.5 Hz). 1H, J = 8.5 Hz), 11.32 (s, 1H); LC-MS m/z 204.09 [M+H]+, calculated value 204.06.

References

[1] Journal of Medicinal Chemistry, 2002, vol. 45, # 3, p. 559 - 562
[2] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 20, p. 5453 - 5463
[3] Patent: WO2012/6068, 2012, A2. Location in patent: Page/Page column 67-68
[4] Monatshefte fuer Chemie, 1921, vol. 42, p. 100
[5] Monatshefte fuer Chemie, 1922, vol. 43, p. 479

Methyl 4-Hydroxyquinoline-2-carboxylate(5965-59-3)Related Product Information

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• Methyl 8-chloro-4-hydroxyquinoline-2-carboxylate
• ETHYL 4-HYDROXY-2-QUINOLINECARBOXYLATE
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• AKOS 223-40
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