Sodium Iodide → 5-Bromo-2-iodo-3-methylpyridine

To a stirred solution of 2,5-dibromo-3-methyl-pyridine (20.0 g, 79.7 mmol, 1 eq) in acetonitrile (120 mL) was added acetyl chloride (8.5 mL, 119.5 mmol, 1.5 eq) followed by addition of NaI (47.8 gm, 319 mmol, 4 eq) at room temperature. Resulting reaction mixture was refluxed for 16 hours. After complete consumption of starting material, reaction mixture was quenched with water (200 mL) and extracted with ethyl acetate (3×200 mL). Organic layer was washed with aqueous sodium bicarbonate (2×300 mL), brine (300 mL) and dried over sodium sulfate. Organic layer was concentrated under reduced pressure to afford brown oil (35.5 g, crude). Crude was purified by column chromatography using silica gel (100-200 mesh). Desired compound was eluted at 5% EtOAc in hexane to get title compound as brown oil (22.5 g, 94.78%). 1H NMR (400 MHz, CDCl3) δ: 2.36 (s, 3H), 7.56 (d, J=2.4 Hz, 1H), 8.24 (d, J=2.28 Hz, 1H). LC-MS (m/z): 297.9 (M+H).

1. customResulting
2. customreaction mixture
3. temperaturewas refluxed for 16 hours
4. customAfter complete consumption of starting material, reaction mixture
5. customwas quenched with water (200 mL)
6. extractionextracted with ethyl acetate (3×200 mL)
7. washOrganic layer was washed with aqueous sodium bicarbonate (2×300 mL), brine (300 mL)
8. dry with materialdried over sodium sulfate
9. concentrationOrganic layer was concentrated under reduced pressure
10. customto afford brown oil (35.5 g, crude)
11. customCrude was purified by column chromatography
12. washDesired compound was eluted at 5% EtOAc in hexane

ORD record

ord-de6a48e668454be3b7b7335888a42fcd

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09131697B2