Isobutyronitrile → 2-(6-Bromopyridin-2-yl)-2-methylpropanenitrile

Temperature

0 °C

A dried 500 mL round bottom flask was charged with a solution of iso-butyronitrile (3.29 g, 4.27 mL, 47.6 mmol) in toluene (100 mL), the solution was cooled down to 0° C. and KHMDS 0.5 m in toluene (100 mL, 50.0 mmol) was added slowly. After complete addition, the reaction mixture was allowed to warm up to room temperature over 1 hour. The resulting mixture was added to a solution of 2,6-dibromopyridine (28.2 g, 119 mmol, available commercially from Aldrich) in toluene (100 mL) While adding, the light yellow solution became quickly dark reddish. The reaction mixture was stirred at room temperature for 18 hours. The crude mixture was diluted with ether, washed with a saturated aqueous solution of ammonium chloride and brine. The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo. The semi-solid residue was suspended in a small amount of toluene and filtered off, the light brown solid corresponded to 2,6-dibromopyridine recovered. Filtrate was purified by flash chromatography (silica gel 50 μm, 220 g, Rediflash Teledyne-Isco) eluting with 0 to 50% over 20 min dichloromethane/hexanes to give 2-(6-bromopyridin-2-yl)-2-methylpropanenitrile (7.608 g, 28.4% yield) as a light yellow oil that solidified into a white solid upon standing. 1H NMR (CHLOROFORM-d) δ: 7.58-7.61 (m, 2H), 7.42-7.46 (m, 1H), 1.76 (s, 6H); LC-MS 225.0 226.9 [M+H]+.

1. additionAfter complete addition
2. temperatureto warm up to room temperature over 1 hour
3. washwashed with a saturated aqueous solution of ammonium chloride and brine
4. dry with materialThe organic phase was dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. filtrationfiltered off
8. customthe light brown solid corresponded to 2,6-dibromopyridine recovered
9. customFiltrate was purified by flash chromatography (silica gel 50 μm, 220 g, Rediflash Teledyne-Isco)
10. washeluting with 0 to 50% over 20 min dichloromethane/hexanes

ORD record

ord-ae54265e4f234691a630f9aa3ea9834e

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901124B2