Methyl iodide → 2-Chloro-3-fluoro-5-iodo-4-methylpyridine

Temperature

-78 °C

To a solution of 2.0 M of lithium diisopropylamide in tetrahydrofuran (5.5 mL) in tetrahydrofuran (20 mL, 200 mmol) at −78° C. was slowly added 2-chloro-3-fluoro-4-iodopyridine (2.589 g, 10.06 mmol) as a solution in tetrahydrofuran (8 mL). The reaction mixture was then stirred at −78° C. for 4 hours. Methyl iodide (0.70 mL, 11 mmol) was then added. After an additional 1 hour, the reaction was then quenched with saturated aqueous NH4Cl and warmed to room temp. The reaction mixture was poured into ethyl acetate and washed sequentially with water and brine, dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (80 g silica, solvent gradient: 0-30% ethyl acetate in heptanes) to yield 2.212 g (57%) of 2-chloro-3-fluoro-5-iodo-4-methylpyridine. LCMS (ESI): M+H=272.0; 1H NMR (500 MHz, CDCl3) δ 8.46 (s, 1H), 2.44 (d, J=1.2 Hz, 3H).

1. customat −78° C.
2. waitAfter an additional 1 hour
3. customthe reaction was then quenched with saturated aqueous NH4Cl
4. temperaturewarmed to room temp
5. additionThe reaction mixture was poured into ethyl acetate
6. washwashed sequentially with water and brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. customevaporated in vacuo
10. customThe crude product was purified via flash chromatography on silica gel (80 g silica, solvent gradient: 0-30% ethyl acetate in heptanes)

ORD record

ord-3e555183c3c34a4f99383bb2729bc7ec

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09206175B2