4-Iodo-2-(trifluoromethyl)pyridine Chemical Properties

Melting point:

24-26 °C

Boiling point:

206.2±35.0 °C(Predicted)

Density 

1.974g/ml

storage temp. 

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

form 

liquid

pka

-0.82±0.20(Predicted)

color 

Clear, colourless to pale yellow

InChI

InChI=1S/C6H3F3IN/c7-6(8,9)5-3-4(10)1-2-11-5/h1-3H

InChIKey

OYQSAEIWDLIZHC-UHFFFAOYSA-N

SMILES

C1(C(F)(F)F)=NC=CC(I)=C1

Safety Information

Hazard Codes 

Xi

HazardClass 

IRRITANT

HS Code 

2933399990

4-Iodo-2-(trifluoromethyl)pyridine Usage And Synthesis

Uses

4-Iodo-2-(trifluoromethyl)pyridine is used as a reagent in the synthesis of aminoisoindoles as β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors which exhibit in vivo brain reduction of β-amyloid peptides.

Reactivity Profile

4-Iodo-2-(trifluoromethyl)pyridine could be cleanly deprotonated by LIDA in tetrahydrofuran at –75 °C[1]. Trapping of the organometallic intermediates with dry ice followed by neutralization gave the 4-iodo-2-(trifluoromethyl)pyridine-3-carboxylic acid (16, 31%). a: LIDA in THF at –75 °C for 2 h; b: (1.) Excess solid carbon dioxide, (2.) Hydrochloric acid.

Synthesis

The general procedure for the synthesis of 4-iodo-2-(trifluoromethyl)pyridine from 3-iodo-2-trifluoromethylpyridine was as follows: a hexane solution (7.2 mL) of 2.5 M butyl lithium was diluted in tetrahydrofuran (30 mL) and cooled to -78 °C in a dry ice/acetone bath. Subsequently, diisopropylamine (2.5 mL) and 3-iodo-2-trifluoromethylpyridine (4.9 g) obtained in Step A were added dropwise to this cooled solution. The reaction mixture was stirred continuously at -78 °C for 2 h. The reaction was subsequently quenched with methanol (2 mL) at the same temperature. The reaction mixture was concentrated and purified by fast column chromatography (silica gel, cyclohexane/ethyl acetate as eluent) to afford 4-iodo-2-(trifluoromethyl)pyridine as yellow acicular crystals (1.6 g, 32% yield). The structure of the product was confirmed by 1H-NMR (CDCl3): δ = 8.40 (d, 1H), 8.06 (s, 1H), 7.90 (d, 1H).

References

[1] Schlosser M, et al. Further Metalations and Functionalizations of Chloro-, Bromo- and Iodo(trifluoromethyl)pyridines. Synthesis, 2004; 10: 1619-1624.

4-Iodo-2-(trifluoromethyl)pyridine (590371-73-6)Related Product Information

• 2,4,6-Collidine
• (Trifluoromethyl)trimethylsilane
• 2-(Trifluoromethyl)pyridine
• 4-Methylpyridine
• 2-Chloro-5-chloromethylpyridine
• 3-(Trifluoromethyl)benzaldehyde
• Azamethiphos
• Trimethylsulfoxonium iodide
• Trifluoromethanesulfonic anhydride
• 4-(Trifluoromethyl)pyridine
• 3-（trifluoromethyl) Cinnamaldehyde
• Pyridine
• 3-Trifluoromethylpyridine
• 4-Iodo-2-methylpyridine
• 2-Iodo-5-trifluoromethylpyridine
• 2-CHLORO-4-IODO-6-(TRIFLUOROMETHYL)PYRIDINE
• Trifluoromethyl
• 3-Chloro-2-iodo-5-(trifluoromethyl)pyridine