Methyl 5-broMo-6-chloropyridine-2-carboxylate

Methyl 5-broMo-6-chloropyridine-2-carboxylate Property

Melting point:

119-121°

Boiling point:

338.8±37.0 °C(Predicted)

Density 

1.684±0.06 g/cm3(Predicted)

storage temp. 

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

pka

-3.38±0.10(Predicted)

Appearance

White to off-white Solid

InChI

InChI=1S/C7H5BrClNO2/c1-12-7(11)5-3-2-4(8)6(9)10-5/h2-3H,1H3

InChIKey

WCWGHRWBXIRYFR-UHFFFAOYSA-N

SMILES

C1(C(OC)=O)=NC(Cl)=C(Br)C=C1

Safety

HS Code 

9999999999

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

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

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

Methyl 5-broMo-6-chloropyridine-2-carboxylate Chemical Properties,Usage,Production

Synthesis

Methyl 5-bromopyridine-2-carboxylate (CAS 29682-15-3, 50 g, 0.23 mol) was mixed with m-CPBA (CAS 937-14-4, 80 g, 0.46 mol) in 400 mL of dry dichloromethane, heated to 60 °C and maintained the reaction for 20 hours. Upon completion of the reaction, the reaction was quenched with saturated sodium sulfite solution followed by extraction with ethyl acetate (2 x 200 mL). The organic layer was washed with brine (2 x 200 mL) and evaporated to dryness. The residue was purified by column chromatography (silica gel, 300 g, with a petroleum ether solution of 15% ethyl acetate as eluent) to give 5-bromo-2-(methoxycarbonyl)pyridine 1-oxide (30 g, 0.13 mol) as a brown oil. The oily substance was slowly added to phosphorus trichloride (CAS 10025-87-3, 80 mL) at 0 °C. The addition process lasted for 1 h. The mixture was then heated to 95 °C and kept for 1 h. The reaction was completed by evaporation. At the end of the reaction, the solvent was removed by evaporation and the residue was dissolved in water (50 mL) and extracted with ethyl acetate (3 x 50 mL). The organic layers were combined and evaporated to dryness to give the white solid product methyl 5-bromo-6-chloropyridine-2-carboxylate (19 g, 59% yield); mass spectrum (EI): m/e = 249.9 [M + H]+.

References

[1] Patent: US2012/316147, 2012, A1. Location in patent: Page/Page column 32
[2] Patent: WO2012/168350, 2012, A1
[3] Patent: WO2014/86806, 2014, A1
[4] Patent: WO2014/86705, 2014, A1
[5] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4266 - 4277