2,6-Difluoropyridine-4-boronic acid Chemical Properties

Boiling point:

334.0±52.0 °C(Predicted)

Density 

1.44±0.1 g/cm3(Predicted)

storage temp. 

Inert atmosphere,Store in freezer, under -20°C

pka

5.46±0.11(Predicted)

form 

powder

color 

White

Safety Information

Hazard Codes 

Xi

Risk Statements 

37/38-41

Safety Statements 

26-39

Hazard Note 

Irritant

HS Code 

2933399990

2,6-Difluoropyridine-4-boronic acid Usage And Synthesis

Synthesis

The final step in the synthesis of 2,6-difluoropyridine-4-boronic acid involves the lithiation of 2,6-difluoro-4-hydrazinylpyridine followed by reaction with triisopropyl borate. This was done as follows: tetrahydrofuran (150 mL) and toluene (400 mL) were added to the reaction flask. Triisopropyl borate (47 g, 0.25 mol) and 4-bromo-2,6-difluoropyridine (44 g, 0.22 mol) were added to the reaction vessel under nitrogen protection and the mixture was cooled to -75 °C. The reaction was carried out in the reaction vessel with the help of a dosing funnel. n-Butyllithium (2.6 M hexane solution, 105 mL, 0.27 mol) was added slowly dropwise through the addition funnel, with the rate of dropwise acceleration controlled to keep the reaction temperature from exceeding -70 °C. After dropwise addition, stirring was continued at -75 °C for 30 min, after which the cooling bath was removed and the reaction mixture was allowed to warm up to -20 °C naturally. The reaction was quenched with 2N hydrochloric acid (~120 mL), pH adjusted to 2, and stirred for 30 minutes. The organic phase was separated and the aqueous phase was extracted twice with ether (250 mL x 2). The organic phases were combined, washed sequentially with water (500 mL) and brine (250 mL), dried over anhydrous magnesium sulfate, decolorized by the addition of activated charcoal for 1 h, filtered through diatomaceous earth and concentrated under reduced pressure. Hexane (250 mL) was added to the residue to precipitate the solid product. The mixture was refrigerated overnight, the solid was collected by filtration, washed with cold hexane and dried. Since 1H NMR analysis showed butylboronic acid impurities in the product, the solid was stirred with hexane (250 mL) at 45 °C for 30 min, hot filtered and washed with cold hexane to give 11.8 g (33% yield) of the target product 2,6-difluoropyridine-4-boronic acid.1H NMR (DMSO-d6, 400 MHz): δ 7.31 (s, 2H).

References

[1] Patent: US7087755, 2006, B1. Location in patent: Page/Page column 5

2,6-Difluoropyridine-4-boronic acid(401816-16-8)Related Product Information

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