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

Temperature

0 °C

n-Butyllithium (46 mL, 0.0738 mol, 1.6 M) was added to a solution of diisopropylamine (10.08 mL, 0.0738 mol) in tetrahydrofuran (80 mL) at −78° C. The reaction mixture was warmed to 0° C., stirred for 30 min, and then cooled to −78° C. 3-Bromo-5-fluoro-pyridine (10.0 g, 0.056 mol) in tetrahydrofuran (10 mL) was added to the reaction mixture and the reaction mixture was stirred for 30 min. Methyl iodide (4 mL, 0.062 mol) was added to the reaction mixture at same temperature and the reaction mixture was then allowed to warm to RT and stirred it for 2 h. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution (150 mL) solution. Then aqueous layer was extracted with ethyl acetate (3×150 mL). The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over sodium sulphate and concentrated to afford 3-bromo-5-fluoro-4-methyl pyridine. 1H NMR (400 MHz, CDCl3) δ 8.49 (s, 1H), 8.31 (s, 1H), 2.38 (s, 3H). MS (M+2): 192.0.

1. temperaturecooled to −78° C
2. stirringthe reaction mixture was stirred for 30 min
3. temperatureto warm to RT
4. stirringstirred it for 2 h
5. customThe reaction mixture was quenched with a saturated aqueous ammonium chloride solution (150 mL) solution
6. extractionThen aqueous layer was extracted with ethyl acetate (3×150 mL)
7. washThe combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL)
8. dry with materialdried over sodium sulphate
9. concentrationconcentrated

ORD record

ord-62b1156a9d5944969ba6a48ac5f52ead

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193724B2