Hexachloroethane → 3-Bromo-4-chloro-5-fluoropyridine

Temperature

-78 °C

To a stirred solution of diisopropylamine (0.48 mL, 0.0034 mol) in dry tetrahydrofuran (10 mL) was added 1.6 M n-butyl lithium in hexane (2.39 mL, 0.00369 mol) drop wise under nitrogen atmosphere at −78° C. and stirred for 30 min at −78° C. To the above stirred mixture was added a solution of 3-bromo-5-fluoropyridine (0.5 g, 0.00284 mol) in dry tetrahydrofuran at −78° C. and stirred for 45 min. After 45 min, a solution of hexachloroethane in dry tetrahydrofuran was added to the above reaction mixture at −78° C. and stirred for 30 min at −78° C. The reaction mixture was slowly warmed to RT and stirred for 1 h. The reaction was quenched with saturated solution of ammonium chloride (10 mL) and extracted with diethyl ether (25 mL x 3). The combined organic layer was washed with water, saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate and evaporated. The obtained crude was purified with silica gel chromatography by hexane to afford the title compound. 1H NMR (400 MHz, CDCl3) δ: 8.58 (s, 1H), 8.43 (s, 1H). MS (M+1): 209.9.

1. stirringstirred for 45 min
2. waitAfter 45 min
3. stirringstirred for 30 min at −78° C
4. temperatureThe reaction mixture was slowly warmed to RT
5. stirringstirred for 1 h
6. customThe reaction was quenched with saturated solution of ammonium chloride (10 mL)
7. extractionextracted with diethyl ether (25 mL x 3)
8. washThe combined organic layer was washed with water, saturated aqueous sodium chloride solution
9. dry with materialdried over anhydrous sodium sulphate
10. customevaporated
11. customThe obtained crude
12. customwas purified with silica gel chromatography by hexane

ORD record

ord-cccfdf14080f43e3a77ba2357b94f76b

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09073929B2