Bromobenzene → 2-Chloro-5-phenylpyridine

Participants

Reaction Conditions

Reaction Steps

In a 300 mL inner volume flask replaced by nitrogen, 30.3 g of tetrahydrofuran solution containing 19.5% by weight of isopropylmagnesium chloride (57.5 mmol as isopropylmagnesium chloride) as a magnesiation reagent was charged, and cooled at 10° C., and then 20 g of tetrahydrofuran solution containing 5-bromo-2-chloropyridine (9.6 g, 50.0 mmol) as a 2,5-dihalogenopyridine derivative (I), was added dropwise in the range of 10 to 20° C. for 1.0 hour. After adding dropwise, the reaction mixture was stirred in the range of 10 to 20° C. for 1.5 hours, and then added dropwise to the solution of tetrahydrofuran (20 g) containing bromobenzene (7.9 g, 50.0 mmol) as a halogenoaryl derivative (II), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.20 g, 0.25 mmol) as a palladium compound in the range of 10 to 20° C. for 2.0 hours. After adding dropwise, the reaction mixture was stirred in the range of 10 to 20° C. for 4.0 hours, and then saturated aqueous solution of ammonium chloride (50 g) was added. Toluene (50 g) was added to the reaction mixture, and after stirring for 1.0 hour, the reaction mixture was left to stand to separate the organic layer. After washing the organic layer with saturated sodium chloride solution (10 g), it was condensed under reduced pressure to obtain crude 6-chloro-3-phenylpyridine (6.5 g, purity: 82%, yield: 60%). The resultant crude 6-chloro-3-phenylpyridine (6.5 g) was purified by silica gel column chromatography (200 g), and 6-chloro-3-phenylpyridine (4.5 g, yield: 42%) as a 6-halogeno-3-arylpyridine derivative (III) was obtained.

Provenance & Evidence