反应详情

温度

10 °C

In a 300 mL inner volume flask replaced by nitrogen, tetrahydrofuran solution of isopropylmagnesium chloride (19.5% by weight, 30.3 g, 57.5 mmol) as a magnesiation reagent was charged, and cooled at 10° C., then tetrahydrofuran solution (20 g) of 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, then the reaction mixture was added dropwise to the solution of tetrahydrofuran (20 g) containing 2-bromopyridine (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, then reaction was stopped by adding saturated aqueous solution of ammonium chloride (50 g), and was left to stand to isolate organic layer. Organic layer was washed with saturated sodium chloride solution (10 g), then condensed under reduced pressure, to obtain crude 6-chloro-3,2′-bipyridine (10.6 g, purity: 81%, yield: 90%). The resultant crude 6-chloro-3,2′-bipyridine (10.6 g) was subjected to simple distillation under reduced pressure (0.9 mmHg, 124° C.), to obtain 6-chloro-3,2′-bipyridine (8.0 g, yield: 68%) as a 6-halogeno-3-arylpyridine derivative (III).

1. additionwas charged
2. additionAfter adding dropwise
3. waitin the range of 10 to 20° C. for 2.0 hours
4. additionAfter adding dropwise
5. stirringthe reaction mixture was stirred in the range of 10 to 20° C. for 4.0 hours
6. customreaction
7. waitwas left
8. customto isolate organic layer
9. washOrganic layer was washed with saturated sodium chloride solution (10 g)
10. customcondensed under reduced pressure
11. customto obtain crude 6-chloro-3,2′-bipyridine (10.6 g, purity: 81%, yield: 90%)
12. distillationThe resultant crude 6-chloro-3,2′-bipyridine (10.6 g) was subjected to simple distillation under reduced pressure (0.9 mmHg, 124° C.)