2-(6-bromopyridin-2-yl)ethanol Chemical Properties

Boiling point:

292.0±25.0 °C(Predicted)

Density 

1.564±0.06 g/cm3(Predicted)

storage temp. 

Inert atmosphere,Room Temperature

pka

14.37±0.10(Predicted)

Safety Information

HazardClass 

IRRITANT

HS Code 

2933399990

2-(6-bromopyridin-2-yl)ethanol Usage And Synthesis

Uses

2-(6-bromopyridin-2-yl)ethanol is used in the preparation of 2,6-diaminopyridine compounds for treating diseases associated with amyloid or amyloid-like proteins, especially ocular diseases.

Synthesis

The general procedure for the synthesis of 2-(6-bromopyridin-2-yl)ethanol from 2-bromo-6-methylpyridine and N,N-dimethylformamide was as follows: first, a hexane solution of 1.6 M n-butyllithium (51 mL, 81.2 mmol) was slowly added to a solution of tetrabutane containing N,N'-diisopropylamine (13.5 mL, 97.4 mmol) and tetrahydrofuran ( 60 mL) in a stirred solution to prepare the LDA solution. The mixture was stirred at 0 °C for 15 min before being cooled to -78 °C and a solution of 2-bromo-6-methylpyridine (5 g, 29.1 mmol) in tetrahydrofuran (90 mL) was added. Stirring was continued at -78 °C for 25 min, followed by the addition of N,N-dimethylformamide (7.9 mL, 107 mmol). After 30 minutes of reaction, methanol (80 mL) and acetic acid (6.1 mL, 132 mmol) were added sequentially. Subsequently, sodium borohydride (1.1 g, 28 mmol) was added at -78 °C and the mixture was stirred overnight and naturally warmed to room temperature. After completion of the reaction, the reaction mixture was diluted with ethyl acetate (150 mL) and washed sequentially with 10% citric acid solution (80 mL) and brine (80 mL). The organic phase was separated and the aqueous phase was extracted with ethyl acetate (2 x 150 mL). The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using dichloromethane/acetone (95/5) as eluent to afford 2-(6-bromopyridin-2-yl)ethanol as a light yellow oil (5 g, 85% yield).1H-NMR (400 MHz, CDCl3): δ=3.01 (t, 2H), 3.09 (t, 1H), 4.02 (q, 2H), 7.16 ( d, 1H), 7.34 (d, 1H), 7.43 (t, 1H).

References

[1] Patent: US2011/92537, 2011, A1. Location in patent: Page/Page column 25-26
[2] Patent: EP2311823, 2011, A1. Location in patent: Page/Page column 26; 28
[3] Patent: WO2011/45383, 2011, A2. Location in patent: Page/Page column 56
[4] Patent: WO2015/110263, 2015, A1. Location in patent: Page/Page column 198