Water → 1-(6-Fluoropyridin-3-yl)ethan-1-ol

Temperature

5 °C

To a stirred mixture of 6-fluoronicotinaldehyde (Frontier Science, 3.14 g, 25.1 mmol) in THF (40 mL) in 250 mL round-bottomed flask, methylmagnesium bromide (Aldrich, 3 M in diethyl ether, 9.21 mL, 27.6 mmol) was added dropwise at about 5 to 10° C. The mixture was stirred at about 5° C. for 30 min. A mixture of water (30 mL) and saturated aqueous ammonium chloride (30 mL) was added slowly and EtOAc (20 mL) was added. The layers were separated. The aqueous phase was extracted with EtOAc (2×60 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (100 g, eluent: EtOAc in hexanes 20% to 70%) to afford (2.30 g, 65% yield) as a clear oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.19 (d, J=1.76 Hz, 1H) 7.85 (td, J=8.07, 2.45 Hz, 1H) 6.92 (dd, J=8.41, 2.93 Hz, 1H) 4.94-5.02 (m, 1H) 2.00 (d, J=3.72 Hz, 1H) 1.53 (d, J=6.46 Hz, 3H). m/z (ESI, positive ion): 142.1 (M+H)+.

1. additionwas added slowly
2. customThe layers were separated
3. extractionThe aqueous phase was extracted with EtOAc (2×60 mL)
4. dry with materialThe combined organic phases were dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe crude product was purified by silica gel column chromatography (100 g, eluent: EtOAc in hexanes 20% to 70%)
8. customto afford (2.30 g, 65% yield) as a clear oil

ORD record

ord-3683a2c133c144129a56ba5d85ed65c8

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772480B2