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 −78° C. 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 SF40-80 g 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, 1H) 7.96 (d, J=1.56 Hz, 1H).

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レコード

ord-5c085d33c4694e2c8e725ba4487b2c3d

出典データセット

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08664401B2