4-Chloropyridine-2-carboxylic acid ethyl ester Chemical Properties

Boiling point:

278.6±20.0 °C(Predicted)

Density 

1.245±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

pka

-0.11±0.10(Predicted)

Appearance

Colorless to light yellow Liquid

Safety Information

HS Code 

2933399990

4-Chloropyridine-2-carboxylic acid ethyl ester Usage And Synthesis

Uses

Ethyl 4-Chloropicolinate is a reactant in the synthesis of 1,5-naphthyridine aminothiazole and pyrazole derivatives as potent and selective inhibitors of the transforming growth factor-β type I receptor, ALK5.

Synthesis

Step-1: Synthesis of ethyl 4-chloropyridine carboxylate: 4-chloropyridine-2-carboxylic acid (20 g, 127 mmol) was mixed with thionyl chloride (200 mL), heated to 100°C and maintained for 6 hours. Upon completion of the reaction, it was cooled to room temperature and the excess thionyl chloride was removed by distillation under reduced pressure. Subsequently, ethanol (200 mL) was slowly added dropwise to the above residue at 0 °C and the resulting mixture was stirred at room temperature for 20 hours. At the end of the reaction, the solvent was removed by evaporation under reduced pressure and the residue was dissolved in ethyl acetate (1000 mL). The organic phase was washed sequentially with water (2 x 500 mL), saturated sodium bicarbonate solution (2 x 500 mL) and brine (500 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to give 21.0 g (89% yield) of the target product ethyl 4-chloropyridinecarboxylate as a semi-solid. The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 8.66 (d, J = 5.0 Hz, 1H), 8.13 (d, J = 2.0 Hz, 1H), 7.49 (dd, J = 5.0 and 2.0 Hz, 1H), 4.47 (q, J = 7.0 Hz, 2H), 1.46 (t, J = 7.0 Hz, 3H); GC -MS (m/z): 185,187 [M+, Cl35,37].

References

[1] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2669 - 2672
[2] Patent: WO2013/164769, 2013, A1. Location in patent: Page/Page column 48
[3] Patent: EP2119706, 2009, A1. Location in patent: Page/Page column 41

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