4-METHOXY-PYRIDINE-2-CARBOXYLIC ACID METHYL ESTER

4-METHOXY-PYRIDINE-2-CARBOXYLIC ACID METHYL ESTER Property

Melting point:

47-50

Boiling point:

280.4±20.0 °C(Predicted)

Density 

1.156±0.06 g/cm3(Predicted)

storage temp. 

Inert atmosphere,Room Temperature

solubility 

DMSO (Slightly), Methanol (Very Slightly)

form 

Solid

pka

2.44±0.10(Predicted)

color 

Pale Yellow

InChI

InChI=1S/C8H9NO3/c1-11-6-3-4-9-7(5-6)8(10)12-2/h3-5H,1-2H3

InChIKey

OJDKENGKKYVJLY-UHFFFAOYSA-N

SMILES

C1(C(OC)=O)=NC=CC(OC)=C1

CAS DataBase Reference

29681-43-4(CAS DataBase Reference)

Safety

Hazard Codes 

Xi

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

2933399990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

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

P405Store locked up.

4-METHOXY-PYRIDINE-2-CARBOXYLIC ACID METHYL ESTER Chemical Properties,Usage,Production

Uses

Methyl 4-methoxypicolinate is a useful intermediate for the synthesis of substituted terpyridine ligands for use in protein purification.

Synthesis

GENERAL STEPS: 2-Pyridinecarboxylic acid (5.0 g, 40.6 mmol) was dissolved in SOCl2 (15 mL) cooled to 0 °C, H2O (950 μL) was added slowly, followed by refluxing the reaction mixture for 1 hour. After the reaction mixture was cooled to room temperature, SOCl2 (15 mL) was added additionally and the reaction was continued to reflux for 2 days. After cooling to room temperature again, a third batch of SOCl2 (15 mL) was added and the mixture was continued to reflux for 2 days. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure and the resulting residue was dissolved in MeOH (30 mL) and refluxed overnight. Subsequently, a solution of NaOMe (4.4 g, 81.2 mmol) in MeOH (50 mL) was added to the reaction system and the reaction was continued at reflux for 2 days. At the end of the reaction, the solvent was removed by distillation under reduced pressure and the residue was dissolved in water and extracted with CHCl3. The organic phases were combined, dried with MgSO4 and concentrated under reduced pressure. The crude product was purified by SiO2 fast column chromatography with the eluent ratio of hexane:AcOEt = 1:1→1:4→1:10 to obtain the target product. Finally, the resulting solid was washed with hexane-Et2O (1:1) to afford methyl 4-methoxypyridine-2-carboxylate (1.8 g, 26% yield) as a light yellow solid.

References

[1] Bulletin of the Chemical Society of Japan, 2015, vol. 88, # 6, p. 784 - 791