2,6-Dimethoxypyridine-3-boronic acid

2,6-Dimethoxypyridine-3-boronic acid Property

Melting point:

128-130°C

Boiling point:

341.2±52.0 °C(Predicted)

Density 

1.26±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

soluble in Methanol

form 

powder or crystals

pka

7.28±0.58(Predicted)

color 

White to Almost white

BRN 

9391039

CAS DataBase Reference

221006-70-8(CAS DataBase Reference)

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38-36/38

Safety Statements 

26-36

WGK Germany 

2

HS Code 

2933399990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

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

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

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

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

P337+P313IF eye irritation persists: Get medical advice/attention.

2,6-Dimethoxypyridine-3-boronic acid Chemical Properties,Usage,Production

Uses

Reactant for:

• Preparation of benzopyranone derivatives as positive GABAA receptor modulators
• Preparation of pyrazine derivatives as orally active corticotropin releasing factor-1 receptor antagonists
• Microwave-enhanced synthesis of trisubstituted pyridazines
• Preparation of biaryl derivatives via palladium-catalyzed Suzuki-Miyaura cross-coupling reaction with aryl- or heteroaryl halides
• Preparation of 3-arylpyridines via palladium-P Phos catalyzed Suzuki cross coupling

Synthesis

Under nitrogen protection, 2,6-dimethoxypyridine (10 g, 71.84 mmol) and N,N-diisopropylethylamine (0.50 mL, 3.59 mmol) were dissolved in dry tetrahydrofuran (200 mL), and cooled to -40°C. The solution of n-butyl lithium (43.10 mL, 86.21 mmol) was added to the solution. At this temperature, n-butyllithium solution (43.10 mL, 86.21 mmol) was added slowly and dropwise. The reaction solution was stirred at -40 °C for 5 min and then slowly warmed to 0 °C and continued to be stirred at this temperature for 3 hours. Subsequently, the reaction solution was cooled again to -40 °C and triisopropyl borate (24.87 mL, 107.76 mmol) was slowly added. After addition, the reaction mixture was brought to room temperature and stirred for 1 hour. Upon completion of the reaction, the reaction was terminated by the addition of water (50 mL), followed by concentration under reduced pressure to remove the organic solvent. To the residue was added 1 M sodium hydroxide solution (100 mL) and the aqueous phase was washed with ethyl acetate (2 x 100 mL). The aqueous phase was adjusted to pH 3 with hydrochloric acid and a solid was precipitated. The solid was collected by filtration and dried to give 2,6-dimethoxypyridine-3-boronic acid (8.10 g, 61% yield). The product was characterized by 1H NMR (DMSO-d6): δ 7.87 (1H, d, J = 7.9 Hz), 6.36 (1H, d, J = 7.9 Hz), 3.90 (3H, s), 3.87 (3H, s).

References

[1] Patent: WO2017/155909, 2017, A1. Location in patent: Paragraph 0111