Triphenylphosphine → 2-(Bromomethyl)pyridine-4-carbonitrile

Bromine (1.07 mL, 20.8 mmol) was added slowly at 0° C. to a solution of triphenylphosphine (5.53 g, 21.1 mmol) in methylene chloride (97 mL). The solution was warmed to room temperature and a white precipitate was observed. 4-Cyano-2-hydroxymethylpyridine 36 (2.61 g, 19.5 mmol) in methylene chloride (20 mL) was added dropwise and the reaction mixture was stirred at room temperature overnight. The reaction mixture was partitioned between water and methylene chloride. The organic layer was washed with saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to give a white solid. Purification by flash column chromatography (silica, 99:1 methylene chloride/methanol) gave 4-cyano-2-bromomethylpyridine (3.95 g), which was used immediately in the next step without further purification: 1H NMR (300 MHz, CDCl3) δ 8.76 (d, J=5.0 Hz, 1H), 7.7 (s, 1H), 7.46 (dd, J=5.0, 1.3 Hz, 1H), 4.58 (s, 2H).

1. customThe reaction mixture was partitioned between water and methylene chloride
2. washThe organic layer was washed with saturated sodium chloride
3. dry with materialdried (sodium sulfate)
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customto give a white solid
7. customPurification by flash column chromatography (silica, 99:1 methylene chloride/methanol)

ORD record

ord-3c8ba7a915c44de9829ac2e16c1ab776

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07727997B2