2-chloro-6-(difluoroMethoxy)pyridine

2-chloro-6-(difluoroMethoxy)pyridine Property

storage temp. 

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

Appearance

Colorless to light yellow Liquid

InChI

InChI=1S/C6H4ClF2NO/c7-4-2-1-3-5(10-4)11-6(8)9/h1-3,6H

InChIKey

MQNNYHKAEYWADV-UHFFFAOYSA-N

SMILES

C1(Cl)=NC(OC(F)F)=CC=C1

Safety

HS Code 

2933399990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H227Combustible liquid

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

2-chloro-6-(difluoroMethoxy)pyridine Chemical Properties,Usage,Production

Synthesis

To a vigorously stirred solution of 6-chloropyridin-2-ol (0.13 g, 1.0 mmol) in acetonitrile (2 mL) was added 6 M aqueous potassium hydroxide (2 mL) at room temperature. Subsequently, difluoromethyl trifluoromethanesulfonate (0.38 mL, 3.0 mmol, 3 equiv) was added slowly and dropwise to the reaction mixture. The temperature was controlled during the reaction by means of a water bath to maintain it at room temperature (note that the reaction is exothermic) and stirring was continued for 30 minutes. Upon completion of the reaction, the mixture was diluted with water (20 mL) and extracted sequentially with ether (2 x 10 mL) and ethyl acetate (3 x 10 mL). The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with the eluent of pentane/diethyl ether (100:0 to 70:30 gradient elution) to afford the pure 2-chloro-6-difluoromethoxypyridine (129 mg, 72% yield). The structure of the product was confirmed by nuclear magnetic resonance hydrogen spectroscopy (1H NMR), carbon spectroscopy (13C NMR), fluorine spectroscopy (19F NMR) and high resolution mass spectrometry (HRMS).

References

[1] Journal of Fluorine Chemistry, 2017, vol. 203, p. 155 - 165