6-Chloronicotinic acid tert-butyl ester Chemical Properties

Melting point:

53-54 °C

Boiling point:

270.7±20.0 °C(Predicted)

Density 

1.173±0.06 g/cm3(Predicted)

storage temp. 

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

pka

-2.13±0.10(Predicted)

Appearance

White to off-white Solid

6-Chloronicotinic acid tert-butyl ester Usage And Synthesis

Synthesis

General procedure for the synthesis of tert-butyl 6-chloronicotinate from 6-chloronicotinic acid and di-tert-butyl dicarbonate: 6-chloronicotinic acid (31.6 g, 200 mmol) and 4-dimethylaminopyridine (2.4 g, 20 mmol) were dissolved in tetrahydrofuran (250 mL), and refluxed for 3 hours. Subsequently, di-tert-butyl dicarbonate (65.0 g, 300 mmol) was slowly added dropwise. After the dropwise addition, the reaction mixture was continued to reflux for 3 hours. After completion of the reaction, the mixture was cooled to room temperature. The solvent was removed by distillation under reduced pressure and the residue was purified by silica gel column chromatography (eluent: ethyl acetate/petroleum ether = 0.1:1 to 1:10) to afford tert-butyl 6-chloronicotinate (40 g, 94% yield) as a white solid. High performance liquid chromatography-mass spectrometry (HPLC-MS, Agilent 1200-6120, column: Waters XBridge C18, 50 mm×4.6 mm×3.5 μm; column temperature: 40 ℃; flow rate: 2.0 mL/min; mobile phase: 95% [water + 10 mM NH4HCO3] and 5% under the initial conditions) was used. acetonitrile, gradient elution to 0% [water + 10 mM NH4HCO3] and 100% acetonitrile over 1.6 min, held for 1.4 min, and finally returned to the initial conditions over 0.1 min, held for 0.7 min) was analyzed for purity, and the results showed that the purity was 100% and the retention time (Rt) = 1.984 min; the calculated value of the mass spectra (MS Calcd.): 213.06; measured value (MS Found): 214.2 [M+H]+. Nuclear magnetic resonance hydrogen spectrum (1H NMR, 400 MHz, DMSO-d6) δ: 1.56 (9H, s), 7.67 (1H, d, J=8.4 Hz), 8.26 (1H, dd, J=8.0,2.4 Hz), 8.86 (1H, d, J=2.4 Hz). Molecular formula: C10H12ClNO2, molecular weight: 213.66. total count of hydrogen in the NMR hydrogen spectral data is 12.

References

[1] Journal of Heterocyclic Chemistry, 2012, vol. 49, # 2, p. 442 - 445
[2] Patent: US2018/215731, 2018, A1. Location in patent: Paragraph 0897; 0909; 0910; 0911; 0912; 0913; 0914
[3] Patent: WO2006/65908, 2006, A1. Location in patent: Page/Page column 67; 68
[4] Organic Process Research and Development, 2011, vol. 15, # 1, p. 64 - 72

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