Iodine → 2,5-Difluoro-4-iodopyridine

Temperature

-20 °C

n-BuLi 2.5M in hexanes (4.9 mL, 12.25 mmol) was added to a solution of diisopropylamine (1.7 mL, 12.20 mmol) in tetrahydrofuran (22 mL) at −20° C., under nitrogen atmosphere, over a period of 10 minutes. The solution was stirred at −20° C. for 30 min and then it was cooled to −78° C. A solution of 2,5-difluoropyridine (1.33 g, 11.5 mmol) in tetrahydrofuran (3 mL) was added over a period of 30 min and the mixture was stirred at −78° C. for 4 hours. After this time, a solution of iodine (3.20 g, 12.6 mmol) in tetrahydrofuran (10 mL) was added dropwise and the mixture was stirred at −78° C. for 1 hour. Water (1 mL) and tetrahydrofuran (3 mL) were added and the temperature was allowed to raise until room temperature, then water (25 mL) and aqueous sodium bisulphite 40% p/v (3 mL) were added. The organic layer was separated and the aqueous layer was extracted with diethyl ether (3×50 mL), the combined organic layers were washed with brine, dried over anhydrous magnesium sulphate and the solvent removed under reduced pressure. The residue was purified by silica flash chromatography (5% diethyl ether in hexanes) to yield the title compound (1.35 g, 48%) as a white crystalline solid.

1. temperatureit was cooled to −78° C
2. stirringthe mixture was stirred at −78° C. for 4 hours
3. stirringthe mixture was stirred at −78° C. for 1 hour
4. temperatureto raise until room temperature
5. customThe organic layer was separated
6. extractionthe aqueous layer was extracted with diethyl ether (3×50 mL)
7. washthe combined organic layers were washed with brine
8. dry with materialdried over anhydrous magnesium sulphate
9. customthe solvent removed under reduced pressure
10. customThe residue was purified by silica flash chromatography (5% diethyl ether in hexanes)

ORD record

ord-8174f2491ed74e569bf384045e9f3188

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258122B2