Methyl iodide → 3-Bromo-5-fluoro-4-methylpyridine

Temperature

0 °C

To the solution of diisopropylamine (10.08 mL, 0.0738 mol) in tetrahydrofuran (80 mL), n-butyl lithium (46 mL, 0.0738 mol, 1.6M), was added at −78° C. and then it was warmed to 0° C. and stirred for 30 min, then it was cooled to −78° C. and the solution of 3-bromo-5-fluoro-pyridine (10.0 g, 0.056 mol) in tetrahydrofuran (10 mL) was added and stirred for 30 min. Methyl iodide (4 mL, 0.062 mol) was added to reaction mixture and allowed to room temperature for 2 h. Reaction mass was quenched with saturated ammonium chloride (100 mL) solution. The aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated to provide the title compound. 1H NMR (400 MHz, CDCl3) δ 8.49 (s, 1H), 8.31 (s, 1H), 2.38 (s, 3H). LCMS (M+3): 192.2.

1. temperatureit was cooled to −78° C.
2. stirringstirred for 30 min
3. waitallowed to room temperature for 2 h
4. customReaction mass
5. customwas quenched with saturated ammonium chloride (100 mL) solution
6. extractionThe aqueous layer was extracted with ethyl acetate (3×100 mL)
7. washThe combined organic extracts were washed with saturated aqueous sodium chloride solution
8. dry with materialdried over sodium sulphate
9. concentrationconcentrated

ORD record

ord-b1ca7f256f374324943de2809acafe20

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09073929B2