Iodine → 2,5-Difluoro-4-iodopyridine

n-Butyllithium (2.5 M in hexanes, 18.6 mL, 46.5 mmol) was added to a solution of diisopropylamine (6.51 mL, 46.1 mmol) in anhydrous tetrahydrofuran (85 mL) at −780C and stirred at this temperature for 1 hour. A solution of 2,5-difluoropyridine (5.0 g, 43 mmol) in anhydrous THF (12 mL) was added dropwise via cannula and the reaction was stirred at −78° C. for 3 hours. After this time, iodine (12.1 g, 47.8 mmol) in tetrahydrofuran (50 mL) was added dropwise via cannula to the reaction at −78° C. and stirred at this temperature for 1 hour after complete addition. Water (100 mL) was added to the reaction and the temperature was allowed to come to RT. The reaction was extracted with diethyl ether (3×100 mL). The combined organics were washed with brine (100 mL), dried (MgSO4), filtered and concentrated. The crude was purified via flash chromatography using an Analogix SF40-80g column and an eluant of ethyl acetate in heptane (0-10%) to afford the title compound as a yellow solid (4.60 g, 44%). LC-MS m/z 242.0 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.39 (t, J=3.71 Hz, 1 H) 7.96 (d, J=1.56 Hz, 1 H).

1. stirringthe reaction was stirred at −78° C. for 3 hours
2. stirringstirred at this temperature for 1 hour
3. additionafter complete addition
4. customto come to RT
5. extractionThe reaction was extracted with diethyl ether (3×100 mL)
6. washThe combined organics were washed with brine (100 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude was purified via flash chromatography

ORD-Eintrag

ord-227ca5d3a81f42b7bc1416572dfa6a67

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08846933B2