2-chloro-3-(difluoroMethoxy)pyridine Chemical Properties

storage temp. 

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

form 

liquid

color 

Clear, faint lemon

InChI

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

InChIKey

HPJAGIYYNJKTOR-UHFFFAOYSA-N

SMILES

C1(Cl)=NC=CC=C1OC(F)F

Safety Information

HS Code 

2933399990

2-chloro-3-(difluoroMethoxy)pyridine Usage And Synthesis

Synthesis

The general procedure for the synthesis of 2-chloro-3-difluoromethoxypyridine from 2-chloro-3-hydroxypyridine and sodium difluorochloroacetate was as follows: according to step 3-i of Scheme 3, 2-chloro-3-hydroxypyridine (Compound 1005, 2.0 g, 15.4 mmol, purchased from Aldrich Chemical Co.) was dissolved in 40 mL DMF and 5.0 mL water in a mixed solvent. Sodium chlorodifluoroacetate (4.71 g, 30.9 mmol, purchased from Lancaster Synthesis, Inc.) and anhydrous potassium carbonate (2.56 g, 18.5 mmol) were then added. The reaction mixture was placed in an oil bath and heated at 100 °C for 2 hours. After that, one equivalent of sodium chlorodifluoroacetate and 1.2 equivalents of potassium carbonate were added and heating was continued for 2.0 hours. After completion of the reaction, the reaction mixture was cooled and the volatiles were removed under reduced pressure. The residue was partitioned between brine and ethyl acetate, and the organic phase was washed once with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The product was purified by silica gel column chromatography using a gradient elution from hexane/DCM to DCM to afford 2-chloro-3-(difluoromethoxy)pyridine (compound 1006, 2.0 g, 72% yield) as a white solid.ESMS (M+H) 180; 1H NMR (CDCl3) δ 8.05 (m, 1H), 7.45 (m, 1H), 6.90 (m, 1H), 6.60 (m, 1H). 1H), 6.60 (t, 1H; J = 75 Hz), 4.01 (s, 3H).

References

[1] Patent: WO2010/96389, 2010, A1. Location in patent: Page/Page column 39-40; 42
[2] Patent: WO2010/135014, 2010, A1. Location in patent: Page/Page column 47-49
[3] Patent: WO2011/87776, 2011, A1. Location in patent: Page/Page column 51; 53
[4] Patent: WO2014/207601, 2014, A1. Location in patent: Page/Page column 88

2-chloro-3-(difluoroMethoxy)pyridine(1206977-80-1)Related Product Information

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• 2-chloro-5-(difluoroMethoxy)pyridine