Bromine → 4-(Bromomethyl)-3,5-dichloro-2,6-difluoropyridine

Temperature

145 °C

To a 1 L 3-neck flask equipped with addition funnel, was placed chlorobenzene (150 ml). 2-(3,5-dichloro-2,6-difluoropyridin-4-yl)acetic acid (21 g, 86.77 mmol) and mercury oxide (20 g, 92.34 mmol) were added in this order. The mixture was heated up to 140-150° C. in an oil bath. Bromine (5.4 mL, 105 mmol) in chlorobenzene (90 ml) was then added dropwise through the addition funnel for 2˜2.5 hr. After the addition of bromine solution, the reaction mixture was refluxed for further 1 hr. and cooled to room temperature. The mixture was filtered through celite pad and the pad was washed with chlorobenzene. The combined filterate was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, ether:hexane (1:10)) to give 20 g (80%) of 4-(bromomethyl)-3,5-dichloro-2,6-difluoropyridine as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 4.66 (2H, s). m/z (EI) 277 (M+).

1. customTo a 1 L 3-neck flask equipped with addition funnel
2. temperaturethe reaction mixture was refluxed for further 1 hr
3. temperatureand cooled to room temperature
4. filtrationThe mixture was filtered through celite pad
5. washthe pad was washed with chlorobenzene
6. customThe combined filterate was evaporated in vacuo
7. customthe residue was purified by silica gel column chromatography (eluent, ether:hexane (1:10))

ORD record

ord-de0cf9edcdf348029b45d5fb66b88ee1

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08106064B2