2-fluoro-5-methylpyridine-3-carboxylic acid

2-fluoro-5-methylpyridine-3-carboxylic acid Property

Boiling point:

309.7±37.0 °C(Predicted)

Density 

1.341±0.06 g/cm3(Predicted)

storage temp. 

Inert atmosphere,Room Temperature

pka

2.61±0.10(Predicted)

Safety

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.

P271Use only outdoors or in a well-ventilated area.

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

2-fluoro-5-methylpyridine-3-carboxylic acid Chemical Properties,Usage,Production

Synthesis

The general procedure for the synthesis of 2-fluoro-5-methylnicotinic acid from 2-fluoro-5-methylpyridine and carbon dioxide is as follows: 1. preparation of intermediate 8: a hexane solution of 1.6 M butyl lithium (28.13 ml, 45 mmol) was slowly added dropwise to a solution of diisopropylamine (6.36 ml, 45 mmol) in tetrahydrofuran (80 ml) at -78°C. After the dropwise addition was completed the mixture was slowly warmed up to 0°C and stirred for 10 minutes at this temperature. 2. the reaction mixture was re-cooled to -78°C and a solution of 2-fluoro-5-methylpyridine (4.64 ml, 45 mmol) in tetrahydrofuran (15 ml) was added slowly dropwise. 3. After stirring the reaction mixture at -78°C for 2 hours, the reaction was terminated by adding an excess of solid carbon dioxide. 4. The reaction mixture was slowly warmed to room temperature and then acidified with 10% citric acid solution and diluted with ethyl acetate. 5. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuum to afford the target compound 2-fluoro-5-methylnicotinic acid as a white solid (4.9 g, 70% yield). 6. The product was characterized as 1H NMR (DMSO-d6, 400MHz) δ 2.34 (3H, s), 8.20-8.26 (2H, m); MS (ES+) 156, (ES-) 154.

References

[1] Organic Letters, 2018,
[2] Patent: WO2008/94992, 2008, A2. Location in patent: Page/Page column 171