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

A solution of lithium di-isopropylamide (2N in tetrahydrofuran/ethylbenzene/heptane, 155 mL, 310 mmol) was added dropwise over 40 minutes to solution of 2-chloro-3-fluoropyridine (31.0 g, 235 mmol) in tetrahydrofuran (200 mL) at −70° C. and the resulting mixture stirred for 4 hours. A solution of iodine (69.0 g, 200 mmol) in tetrahydrofuran (100 mL) was added dropwise over 30 minutes and the resultant mixture was stirred for 30 minutes at −70° C. then allowed to warm to room temperature over 1 hour. The reaction mixture was poured onto aqueous sodium metabisulphite solution (20% w/v, 2 L) and extracted with diethyl ether (3×300 mL). The combined organic extracts were washed with aqueous sodium metabisulphite solution (20% w/v, 2 L) and water (200 mL), dried over Na2SO4 and evaporated under reduced pressure to yield an oil. The resultant oil was triturated with diethyl ether to yield the title compound as a red/brown solid (28 g, 46% yield). 1H NMR (400 MHz, CDCl3): δ 7.87 (d, J=5.0 Hz, 1H), 7.66 (ddd, J=5.0, 4.0, 0.4 Hz, 1H).

1. extractionextracted with diethyl ether (3×300 mL)
2. washThe combined organic extracts were washed with aqueous sodium metabisulphite solution (20% w/v, 2 L) and water (200 mL)
3. dry with materialdried over Na2SO4
4. customevaporated under reduced pressure
5. customto yield an oil
6. customThe resultant oil was triturated with diethyl ether

ORD record

ord-16ccc74216964fdf9baab4e0facfff7f

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697708B2