Dimethylformamide → (5-Fluoropyridin-2-yl)methanol

Temperature

-78 °C

At −78° C. under nitrogen, add n-butyllithium (2.5 M in hexane, 16.4 mL, 40.9 mmol) via syringe to a solution of 2-bromo-5-fluoro-pyridine (6.0 g, 34.1 mmol) in toluene (220 mL), while keeping the reaction temperature below −60° C. Stir the mixture at −78° C. and then add DMF (3.4 mL, 44.3 mmol) and stir for 1 h at this temperature. Warm to −10° C. and quench with methanol (10 mL). Concentrate the mixture to half of the volume in vacuo. Dilute with methanol (150 mL), cool the mixture to −78° C. and add sodium borohydride (3.2 g, 85.2 mmol) portion wise over 5 min. Warm the mixture to ambient temperature and stir for 2 h. Quench with water (10 mL) and remove the organic solvent in vacuo to obtain an oil/water mixture. Extract with diethyl ether (3×100 mL), dry the combined organic extracts, wash with brine, dry and concentrate in vacuo to obtain the desired intermediate as an oil (3.9 g, 91%).

1. customthe reaction temperature below −60° C
2. temperatureWarm to −10° C.
3. customquench with methanol (10 mL)
4. concentrationConcentrate the mixture to half of the volume in vacuo
5. additionDilute with methanol (150 mL)
6. temperaturecool the mixture to −78° C.
7. temperatureWarm the mixture to ambient temperature
8. stirringstir for 2 h
9. customQuench with water (10 mL)
10. customremove the organic solvent in vacuo
11. customto obtain an oil/water mixture
12. extractionExtract with diethyl ether (3×100 mL)
13. customdry the combined organic extracts
14. washwash with brine
15. customdry
16. concentrationconcentrate in vacuo

ORD record

ord-6119ad4c562b45539f9451a8f00b5d14

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08022062B2