1-(3-Fluoro-pyridin-4-yl)-ethanol

Synthesis

To a stirred solution of 3-fluoropyridine (14 g, 144.2 mmol) in anhydrous THF (150 mL), cooled to -78°C under argon protection, a n-heptane/THF/ethylbenzene solution (79.2 mL, 158.6 mmol) of lithium 2 N diisopropylammonium (LDA) was added slowly dropwise over a period of about 1 hour. After stirring for 2.5 hours, a solution of acetaldehyde (8.9 mL, 158.5 mmol) in 25 mL of anhydrous THF cooled to about 0°C was added slowly dropwise and the reaction mixture was continued to be stirred at -78°C for 1.5 hours. Subsequently, the reaction solution was slowly warmed to -30 °C and the reaction was quenched by the addition of a solution of ammonium chloride (150 g) in 700 mL of water. The mixture was extracted with ethyl acetate (3 x 400 mL) and the combined organic layers were washed with brine (4 x 200 mL) and dried over anhydrous sodium sulfate. After concentrating the organic phase, the residual oily material was crystallized with hexane (40 mL) to give 15.6 g (76% yield) of 1-(3-fluoropyridin-4-yl)ethanol.

References

[1] Patent: WO2005/13986, 2005, A1. Location in patent: Page/Page column 44
[2] Patent: US2007/142414, 2007, A1. Location in patent: Page/Page column 18-19
[3] Patent: WO2007/96334, 2007, A1. Location in patent: Page/Page column 31-32
[4] Tetrahedron, 1983, vol. 39, # 12, p. 2009 - 2021