Iodine → 2-Chloro-3-fluoro-4-iodopyridine

Temperature

-78 °C

In an oven-dried flask, to a solution of 2.0 M of lithium diisopropylamide in tetrahydrofuran (6.0 mL) in tetrahydrofuran (30 mL, 400 mmol) at −78° C. was added 2-chloro-3-fluoropyridine (1.000 mL, 10.06 mmol). The resulting mixture was stirred at −78° C. for 2 hours. Iodine (3.899 g, 15.36 mmol) was then added as a solution in 5 mL tetrahydrofuran and the reaction was maintained −78° C. for an additional 2.5 hours. 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 10% aqueous Na2S2O3 and brine, dried over MgSO4, filtered, and evaporated in vacuo to yield 2.7279 g (100%) of 2-chloro-3-fluoro-4-iodopyridine. LCMS (ESI): M+H=258.0; 1H NMR (500 MHz, CDCl3) δ 7.87 (d, J=4.9 Hz, 1H), 7.71-7.59 (m, 1H).

1. temperaturethe reaction was maintained −78° C. for an additional 2.5 hours
2. customThe reaction was then quenched with saturated aqueous NH4Cl
3. temperaturewarmed to room temp
4. additionThe reaction mixture was poured into ethyl acetate
5. washwashed sequentially with 10% aqueous Na2S2O3 and brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. customevaporated in vacuo

ORD record

ord-d312eae25766406f933121b06ce60451

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08623889B2