2,6-Dibromopyridine → 6-Bromopyridine-2-carbonitrile

Temperature

0 °C

n-Butylmagnesium chloride (3.49 mmol) in 2.05M tetrahydrofuran solution (1.70 mL) was added to ice-cooled n-butyllithium (7.03 mmol) in 1.45M hexane (4.85 mL). The mixture was stirred at 0° C. for 15 minutes, and cooled to −10° C. to give a suspension. 2,6-Dibromopyridine (2.37 g, 10 mmol) in toluene (25 mL) was added to the suspension below −5° C. over a period of 10 minutes or more. The mixture was stirred at −10° C. for 3 hours, and p-toluenesulfonyl cyanide (2.48 g, 13.3 mmol) was added. After the mixture was stirred at 0° C. for 30 minutes, an aqueous solution (15 mL) of 1M acetic acid was added thereto. The reaction mixture was extracted twice with ethyl acetate (50 mL). The organic extracts combined were washed with an aqueous saturated solution (15 mL) of sodium chloride, dried over magnesium sulfate, and purified by flash column chromatography on silica gel in a developing solvent system of hexane-ethyl acetate (10:1, v/v) to give the title compound (942 mg, about 51% yield) as orange powder.

1. temperaturecooled to −10° C.
2. customto give a suspension
3. stirringThe mixture was stirred at −10° C. for 3 hours
4. stirringAfter the mixture was stirred at 0° C. for 30 minutes
5. extractionThe reaction mixture was extracted twice with ethyl acetate (50 mL)
6. washThe organic extracts combined were washed with an aqueous saturated solution (15 mL) of sodium chloride
7. dry with materialdried over magnesium sulfate
8. custompurified by flash column chromatography on silica gel in a developing solvent system of hexane-ethyl acetate (10:1

ORD record

ord-a0a163a1aff14890aab17d7f8c8e5cba

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06946559B2