4,6-DICHLORO-2-METHYL-NICOTINIC ACID ETHYL ESTER

4,6-DICHLORO-2-METHYL-NICOTINIC ACID ETHYL ESTER Property

Boiling point:

283℃

Density 

1.320

Flash point:

125℃

storage temp. 

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

pka

-0.22±0.10(Predicted)

Appearance

Colorless to light yellow Liquid

InChI

InChI=1S/C9H9Cl2NO2/c1-3-14-9(13)8-5(2)12-7(11)4-6(8)10/h4H,3H2,1-2H3

InChIKey

LNIMLSAAPISOEC-UHFFFAOYSA-N

SMILES

C1(C)=NC(Cl)=CC(Cl)=C1C(OCC)=O

Safety

HS Code 

2933399990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H332Harmful if inhaled

H335May cause respiratory irritation

Precautionary statements

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

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

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.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P321Specific treatment (see … on this label).

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

P501Dispose of contents/container to..…

4,6-DICHLORO-2-METHYL-NICOTINIC ACID ETHYL ESTER Chemical Properties,Usage,Production

Synthesis Reference(s)

[1] Compounds for the prevention and treatment of cardiovascular diseases. Patent no. US20080188467A1.

Synthesis

A mixture of malonic acid (20 g, 192 mmol), 2,4,6-trichlorophenol (72 g, 365 mmol), and phosphorus oxychloride (38 mL, 403.2 mmol) was stirred at reflux for 12 h. The reaction mixture was cooled to 70° C. and poured into ice water. The solid was collected by filtration, washed with water, and dried to give malonic acid bis-(2,4,6-trichloro-phenyl)ester (85 g, 95%). A solution of malonic acid bis-(2,4,6-trichloro-phenyl)ester (85 g, 184 mmol) and ethyl 3-aminocrotonate (26.08 g, 201.9 mmol) in bromobenzene (100 mL) was stirred at reflux for 50 min. The reaction mixture was cooled to 50° C. and diluted with EtOAc (260 mL). The solid was collected by filtration, washed with water, and dried to give 4,6-dihydroxy-2-methyl nicotinic acid ethyl ester (31 g, 86%). A solution of 4,6-dihydroxy-2-methyl nicotinic acid ethyl ester (31 g, 157 mmol) in phosphorus oxychloride (60 mL, 629 mmol) was stirred at reflux for 1.5 h. The extra phosphorus oxychloride was removed and the reaction mixture was poured into ice water. The solid was removed by filtration. The filtrate was extracted with dichloromethane (3×100 mL) and concentrated. The residue was further purified by column chromatography, to yield 4,6-dichloro-2-methyl nicotinic acid ethyl ester (16.9 g, 46%).

References

[1] Patent: WO2011/87776, 2011, A1. Location in patent: Page/Page column 64; 66
[2] Patent: WO2007/16525, 2007, A2. Location in patent: Page/Page column 94-96; 101-103
[3] Patent: US2008/188467, 2008, A1. Location in patent: Page/Page column 26-27; 29-30; 40-41
[4] Patent: US2013/281397, 2013, A1. Location in patent: Paragraph 0451; 0465
[5] Patent: CN103319408, 2016, B. Location in patent: Paragraph 0402-0405