Thionyl Chloride → 4-Chloro-2-(chloromethyl)pyridine

Temperature

60 °C

4-Chloro-2-pyridinemethanol (1.0 g, 6.965 mmol) was dissolved in dichloromethane (25 cm3), heated to reflux and then treated slowly with a solution of thionyl chloride (1.50 cm3, d=1.631 gcm−3, 0.0206 mmol) in DCM (25 cm3). The reaction mixture was then stirred at 60° C. for 3 h, soon turning pink. After this time the DCM was evaporated off and the pale pink residue carefully neutralised with saturated sodium bicarbonate solution (40 cm3). The product was then extracted into DCM (3×30 cm3) and dried over sodium carbonate for 30 min. After filtration the product solution was then concentrated to a low volume and filtered through a short silica column (1:4 methanol/DCM as eluent), giving a pale yellow solution. This was then concentrated down to a red/brown oil, dried at 50° C., which was the desired product 4-chloro-2-chloromethylpyridine (934 mg, 83%); 1H NMR (CDCl3); δH 8.40 (d, 1H, J=5.5), 7.44 (d, 1H, J=1.5), 7.19 (dd, 1H, J=5.5, 1.5), and 4.58 (s, 2H) ppm.

1. temperatureheated
2. temperatureto reflux
3. customAfter this time the DCM was evaporated off
4. extractionThe product was then extracted into DCM (3×30 cm3)
5. dry with materialdried over sodium carbonate for 30 min
6. filtrationAfter filtration the product solution
7. concentrationwas then concentrated to a low volume
8. filtrationfiltered through a short silica column (1:4 methanol/DCM as eluent)
9. customgiving a pale yellow solution
10. concentrationThis was then concentrated down to a red/brown oil
11. customdried at 50° C.

ORD record

ord-aa3df7e3bb0b4f57a46dfc238f07ecad

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08647781B2