alpha-2-pyridylpyridine-2-methanol

Synthesis

The general procedure for the synthesis of bis(pyridin-2-yl)methanol from pyridine-2-carbaldehyde and 2-bromopyridine is as follows: Step A - Synthesis of di(pyridin-2-yl)methanol: To a solution of 2-bromopyridine (3.0 g, 19.0 mmol) in 60 mL of THF was slowly added n-butyllithium (2.5 M in hexane, 7.6 mL, 19.0 mmol) at -78 °C. The reaction mixture was stirred at -78 °C for about 15 min, then pyridine-2-carbaldehyde (2.17 mL, 22.8 mmol) was added slowly dropwise at the same temperature. After the dropwise addition was completed, stirring was continued at -78 °C for 30 min, then gradually warmed up to room temperature and stirred for 2 hours. Upon completion of the reaction, the reaction was quenched with saturated aqueous NH4Cl solution. The reaction mixture was diluted with ethyl acetate and the organic layer was separated and the aqueous layer was back-extracted twice with ethyl acetate. All organic phases were combined, washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give bis(pyridin-2-yl)methanol in 70% yield as a yellow oil.

References

[1] Synlett, 2006, # 16, p. 2553 - 2558
[2] Synlett, 2008, # 9, p. 1418 - 1422
[3] Patent: WO2008/130581, 2008, A1. Location in patent: Page/Page column 181
[4] Journal of Organic Chemistry, 1993, vol. 58, # 16, p. 4382 - 4388